Patent ID: 12209954

While the invention is described with reference to the above drawings, the drawings are intended to be illustrative, and other embodiments are consistent with the spirit, and within the scope, of the invention.

DETAILED DESCRIPTION

The various embodiments now will be described more fully hereinafter with reference to the accompanying drawings, which form a part hereof, and which show, by way of illustration, specific examples of practicing the embodiments. This specification may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this specification will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. Among other things, this specification may be embodied as methods or devices. Accordingly, any of the various embodiments herein may take the form of an entirely hardware embodiment, an entirely software embodiment or an embodiment combining software and hardware aspects. The following specification is, therefore, not to be taken in a limiting sense.

FIG.1is a high-level diagram illustrating portions of a sample separation and identification instrument1000including an optical detection system in accordance with one embodiment of the present invention. In the illustrated embodiment, instrument1000is a capillary electrophoresis (CE) instrument comprising at least one capillary101having an outer capillary diameter and an inner capillary channel diameter of a capillary channel through which a sample or other liquid may flow.

With additional reference toFIG.2, instrument1000comprises an optical detection system200comprising sources201,202,203, and204. As used herein, unless otherwise indicated or implied, “source” refers to a source of electromagnetic radiation, for example, a source of ultra-violet (UV) radiation, visible light, near-infrared, and/or infrared radiation. The terms “UV source” and “UV light source” will be used interchangeably herein to mean a source producing radiation primarily or exclusively within UV band of the electromagnetic spectrum, e.g., from about 10 nanometers (“nm”) to 400 nm. As used herein the term “visible light source” means a source producing radiation primarily or exclusively within visible light band of the electromagnetic spectrum (e.g., from about 380 nm to 740 nm).

In the illustrated embodiment, source201comprises a first UV source providing UV beam b1having a first wavelength or wavelength band and source204comprises a second UV source providing UV beam b4having a second wavelength or wavelength band. Source203comprises a visible light source providing visible light beam b3. Source202comprises a third UV source providing UV beam b2having wavelength or wavelength band that may be the same or different than that of either beam b1or b4. In one embodiment, beam b1has a nominal or peak output at a wavelength that is at or near 220 nm and beam b4has a nominal or peak output at a wavelength that is at or near 280 nm. Beam b2may have a nominal or peak output at a wavelength that is different from or the same as that of beam b1and/or beam b4. In alternative embodiments, these wavelengths might be different without departing from the spirit and scope of the invention. In a preferred embodiment, UV sources201,202, and204each comprise a UV laser or similar UV source. In certain alternative embodiments, sources201,202, and204may comprise a deuterium lamp, a UV light emitting diode (LED), or the like.

In one embodiment, sources201,202, and/or204may be configured to provide a UV light that can be focused to provide a beam or spot at or near each capillary101having a diameter that is equal or approximately equal to an inner capillary diameter, preferably a diameter at or near the capillary that is less than the inner capillary diameter. It has been found that transmittance or absorption measurements can be made with better sensitivity with the use of a smaller beam/spot diameter at or near the capillary because, for example, a higher percentage of the beam is impacted by variations in transmittance or absorption of the sample, sample solution or other substance flowing through the inner capillary channel.

In a preferred embodiment, sources201,202,203and/or204are point sources. As used herein, the term “point source” refers to a source that produces a beam that can be focused to a spot (cross-section or slice of the beam at a particular location) at or near a capillary having a beam diameter that is less than or equal to the diameter of an inner channel of the capillary. As used herein, in the case of a source producing a beam having, or characterized by, a Gaussian shape (e.g., a laser source), the term “beam diameter” means the 1/e2diameter of the beam at a particular location along the beam's optical path (e.g., at capillary101). As used herein, in the case of a source producing a beam not having, or not characterized by, a Gaussian shape, the term “beam diameter” means a diameter of the smallest circle or aperture containing 85% of the energy or power in a cross-section of the beam at a particular location in the beam's optical path (e.g., at a capillary101).

Source203comprises a visible light source providing visible light beam b3, for example, light having a nominal or peak output at a wavelength at or near 505 nm or some other wavelength within the visible light range. In some embodiments, source203is a visible broadband light source or a white light source. In certain embodiments, source203and beam b3may further comprise at least some radiation in the UV and/or infrared wavelength band ranges. Source203and beam b3may comprise a range of wavelengths, for example, a wavelength range suitable for exciting a plurality of dyes excited at different wavelengths (e.g., a wavelength range over all or part of the visible light wavelength range or a wavelength range also including radiation in the infrared and/or ultraviolet wavelength band). In certain embodiments, source203may comprise electromagnetic radiation in visible band, as well as in the ultraviolet, infrared, and/or near-infrared with sufficient energy to excite dyes sensitive to radiation in each of these ranges. Source203may comprise one or more of an incandescent lamp, a gas discharge lamp (e.g., Halogen lamp, Xenon lamp, Argon lamp, Krypton lamp, etc.), a light emitting diode (LED), a white light LED, an organic LED (OLED), a laser (e.g., chemical laser, excimer laser, semiconductor laser, solid state laser, Helium Neon laser, Argon laser, dye laser, diode laser, diode pumped laser, fiber laser, pulsed laser, continuous laser), or the like.

Simultaneous illumination of multiple capillaries for UV transmittance or absorption measurements at the same UV wavelength has previously required the use of multiple UV sources such as a deuterium lamp, for example, in combination with a plurality of optical fibers located in front of a plurality of corresponding capillaries. There are various reasons for this. A typical deuterium lamp used in the art for UV absorption measurements in the CE context is very stable (low noise), but has limited power. In a multiple capillary UV absorption measurement system, it is generally important to limit crosstalk between adjacent capillaries. This may be achieved by using a small illumination spot size in each capillary relative to the capillary's cross-sectional area. With a deuterium lamp UV source, this typically requires use of a pinhole mask (or other mask) and/or fiber optics to achieve a sufficiently compact system. However, much of the lamp's power is wasted in such systems and/or multiple lamps are needed to sufficiently illuminate multiple capillaries. Also, because deuterium lamps have a broad-spectrum output of incoherent radiation, it is generally not possible to focus a beam down to a dimension that is less than or equal to the capillary channel diameter.

Some preferred embodiments of the invention disclosed herein solve the above problems by utilizing a UV laser or other UV source characterized by high intensity or power, narrow wavelength band, and/or coherent emission. One embodiment uses a UV laser that is approximately 100 times brighter than a typical deuterium lamp and is able to provide beam that may be focused to a spot at which the beam diameter is less than or equal to the inner channel diameter of a capillary, yet with a small numerical aperture or divergence. Thus, the initial illumination power of the UV laser source is greater than in prior systems using deuterium lamps and has more favorable optical characteristic (e.g., small focus diameter and divergence). Also, because a UV laser source can produce a beam with a much smaller diameter and numerical aperture than does a deuterium UV lamp, a sufficiently small illumination spot size on each capillary can be achieved using focusing rather than having to rely on, for example, a pinhole mask or fiber optic array. Thus, much less of the source's illumination power is wasted and the sensitivity to variations in transmittance/absorption of a capillary sample is improved, since all or most of the beam energy is transmitted through the inner capillary channel. Thus, some embodiments of the invention implement optics that divide a single UV laser beam into multiple beamlets and that then direct and focus respective beamlets onto respective capillaries with a sufficiently small illumination spot size to avoid cross talk and with sufficient illumination power for obtaining usable transmittance or absorption measurements. In some embodiments, the multiple beamlets are optically coupled to or received by a fiber array having a plurality of optical fibers. In some embodiments, other UV sources with these favorable characteristics may be used instead of, or in addition to, a UV laser (e.g., a UV light emitting diode).

A challenge to using UV lasers in CE applications, rather than deuterium lamps, is that lasers typically have a much higher source noise level. However, in some embodiments disclosed herein, this problem is addressed using a reference capillary and a corresponding reference beam. Additionally, as will be further described below, detected electromagnetic radiation (e.g., UV radiation) from the reference beam may be used by a digital signal processing unit to reduce or remove noise from detected radiation of the other beams (corresponding to capillaries containing sample substances).

Tables 1-3 show optical characteristic of a UV laser having a Gaussian beam shape. Such beams may be used, for example, with capillaries having inner capillary channel diameters in the range of 50 micrometers to 200 micrometers to achieve the above discussed advantages.

TABLE 1Laser beam wavelength (nm)220280Beam waist Diameter (um)1010Numerical Aperture0.01400.0178Divergence (at z = zR; radians)0.02800.0357Divergence (at z = zR; degrees)1.602.04

TABLE 2Laser beam wavelength (nm)220280Beam waist Diameter (um)2020Numerical Aperture0.00700.0089Divergence (at z = zR; radians)0.01400.0178Divergence (at z = zR; degrees)0.801.02

TABLE 3Laser beam wavelength (nm)220280Beam waist Diameter (um)4040Numerical Aperture0.00350.0045Divergence (at z = zR; radians)0.00700.0089Divergence (at z = zR; degrees)0.400.51

In some embodiments, instrument1000further comprises optical fiber arrays251and261. A fiber array comprises a plurality of optical fibers arranged in a particular manner. For example, a fiber array may include fibers arranged in a row or an approximate straight line. As another example, a fiber array may include fibers arranged in a bundle (e.g., fibers at least partially enclosed with a tube or a circular-shaped enclosure). An optical fiber can be made by, for example, glass or plastic. An optical fiber can receive appropriately directed light at one end, and guide it to another end of the optical fiber with minimum, negligible, or no loss of light. As illustrated inFIG.2, optical fiber array251can be arranged to receive UV beamlets obtained from beam b1of source201and/or beam b4of source204. Optical fiber array251delivers the received UV beamlets to pass through certain locations within the capillaries101for UV transmittance or absorption measurements. The UV beamlets that pass through capillaries101, also referred to as the transmitted UV beamlets, are received by optical fiber array261. Optical fiber array261delivers the received UV beamlets to a detector module290. These beamlets are subsequently imaged onto a detector291in the detector module290for UV transmittance or absorption measurements.

Instrument1000further comprises optical detectors291,292, and293and digital signal processing unit298. Instrument1000may be adapted to either incorporate or be communicatively coupled with a user device280, which comprises a processor, memory, storage, display, and/or user interface components (e.g. a display, keyboard and/or touch screen, etc.) allowing a user to receive, use, and/or display data generated by instrument1000and, in some embodiments, control and/or configure aspects of instrument1000. Digital signal processing (DSP) unit298processes signals from one or more of detectors291-293to, among other things, remove signal noise to help the instrument and user device obtain data usable for determining and displaying transmittance/absorption and/or fluorescence measurements corresponding to substances processed by the instrument. It should be noted that, in various embodiments, a DSP unit such as DSP unit298might be implemented in hardware, software, or a combination of hardware and software. Also, a DSP unit might be implemented on a connected user device and/or within a detection subsystem or other subsystem of the instrument itself.

Optical detectors291,292, and293may comprise one or more individual photodetectors including, but not limited to, photodiodes, photomultiplier tubes (PMTs), semiconductor detectors, multiple channel PMTs, or the like. Additionally, or alternatively, optical detectors291,292, and293may comprise an array sensor including an array of sensors or pixels. The array sensor may comprise one or more of a complementary metal-oxide-semiconductor (CMOS) sensor, a charge-coupled device (CCD) sensor, a plurality of photodiodes detectors, a plurality of photomultiplier tubes, or the like. In certain embodiments, one or more of optical detectors291,292, and293may comprise a spectrometer comprising an array detector and a dispersive element such as a reflection or transmission diffractive grating that spread incoming radiation into a spectrum across the detector array.

Sources201-204, detectors291-293, fiber arrays251and261, and DSP unit298are part of an optical detection subsystem of instrument1000. Other components of the optical detection system include various optical components arranged to provide various optical paths for beams travelling from sources201-204to detectors291-293. Those optical components and optical paths are illustrated and described below in the context ofFIGS.2-6and accompanying text, but are not separately shown inFIG.1.

In summary, instrument1000operates as follows: A sample mixture or solution containing various samples or sample molecules is prepared in or delivered into a sample source container105. At least a portion of the sample mixture is introduced into one end of capillaries101, for example, at the cathode103using a pump or syringe (not separately shown) or by applying a charge or electric field to capillaries101. With the sample solution loaded into the cathode end of a capillary101, voltage supply104creates a voltage difference between cathode103and anode102. The voltage difference causes negatively charged, dye-labeled samples to move from sample source container105to sample destination container106. Longer and/or less charged dye-labeled samples move at a slower rate than do shorter and/or higher charged dye-labeled samples, thereby creating some separation between samples of varying lengths and/or charges. Beams originating from UV source201, UV source202, visible light source203, and/or UV source204pass through a location within the capillaries101. Beams used for UV transmittance or absorption measurements are delivered by fiber array251, subsequently pass through capillaries101, and are received by fiber array261. The transmitted beams are subsequently imaged onto detector291. Fluorescence resulting from a UV beam exciting substance in capillaries101is directed to detector292. Fluorescence resulting from a visible light beam exciting substance in capillaries101is directed to detector293. In certain embodiments, UV source201and/or UV source204may be replaced or supplemented by sources including other wavelength bands, for example, visible light, infrared, or near-infrared bands, for the purpose of making transmittance or absorption measurements within those wavelength bands.

Signals are provided from one or more of detectors291-293to DSP unit298for processing. Among other things, DSP unit298is configured to utilize signals corresponding to a reference capillary101to reduce noise in signals corresponding to other capillaries101through which samples to be measured pass. The output from DSP298is used by user device280or similar device to further process and display measurement results corresponding to measured samples.

FIG.2shows optical detection system200of instrument1000ofFIG.1in accordance with an embodiment of the invention. The illustrated components provide multiple optical pathways from sources201,202,203, and204to capillaries101. InFIG.2, a cross section of nine different capillaries101is shown. From the perspective of the illustrations inFIGS.2,3, and6A, capillaries101extend longitudinally along a dimension orthogonal to the illustration (i.e., into and out of the page).

The relevant optical pathways and optical components illustrated inFIG.2will now be described in further detail, starting with the pathway from UV source201to detector291.

Beam b1and/or Beam b4: UV Absorption Measurement

As illustrated inFIG.2, UV source201emits UV beam b1. Beam b1passes through diffractive optical element211, which operates to split beam b1into nine beamlets that may be collimated or approximately collimated using a lens212. Diffractive optical element211may be optionally configured to otherwise condition the beamlets, for example, configured to change the convergence or divergence of one or more of the beamlets from that of beam b1. In the illustrated embodiment, lens212further focuses one or more of the nine beamlets such that they can be aligned to the corresponding fibers of fiber array251. In the illustrated embodiment, these beamlets are reflected by mirror213and received by fiber array251.

In some embodiments, UV beams with two different wavelengths are used for UV absorption measurements. For example, as illustrated inFIG.2, an additional UV source204emits UV beam b4. Beam b4passes through diffractive optical element233, which operates to split beam b4into nine beamlets that may be collimated or approximately collimated using a lens234. Diffractive optical element233may be optionally configured to otherwise condition the beamlets, for example, configured to change the convergence or divergence of one or more of the beamlets from that of beam b4. As described above, the beamlets originated from beam b1are optionally reflected by mirror213. The reflected beamlets originated from beam b1pass through a dichroic beam combiner235. The beamlets originated from beam b4are also directed toward dichroic beam combiner235. Dichroic beam combiner235combines beamlets originating from beam b1of UV source201, which operates at a first wavelength, and beamlets originating from beam b4of UV source204, which operates at a second wavelength. In some embodiments, lens234further focuses one or more of the nine beamlets originated from beam b4such that they can be aligned to corresponding fibers of fiber array251. The combined beamlets having two different wavelengths are then aligned with and received by the corresponding fibers of fiber array251.

Fiber array251delivers the UV beamlets, originated from one or both beams b1and b4, to capillaries101. The UV beamlets then pass through capillaries101. In the illustrated embodiment, eight of the capillaries contain samples to be measured and the ninth capillary is used as a reference. The UV beamlets from beam b1and/or beam b4passing through capillaries101are used to measure absorption and/or transmittance, wherein a portion of each beamlet's power is absorbed by a corresponding sample-filled capillary101and another portion transmits through the corresponding capillary101. In certain embodiments, a smaller portion of a reference beamlet's power is absorbed by a reference capillary101than through some or all of the remaining capillaries.

FIG.3illustrates certain additional details regarding optical elements for beamlets coupling from fiber array251to capillaries101in the optical detection system200ofFIG.2. In some embodiments, a lenslet array and a plurality of UV beamlet masks are disposed between fiber array251and capillaries101. As illustrated inFIG.3, a lenslet121and a UV beamlet mask131are disposed between fiber251-1and capillary101-1. As illustrated, respective other lenslets and UV beamlet masks are similarly disposed (but not separately numbered) between respective other fibers (251-2,251-2,251-3,251-4,251-5,251-6,251-7, and251-8, and251-ref) and capillaries (101-2,101-3,101-4,101-5,101-6,101-7,101-8,101-ref).

As illustrated inFIGS.2and3, fiber251-1directs a UV beamlet (e.g., a beamlet originated from beam b1and/or beam b4) to lenslet121. Lenslet121focuses the UV beamlet onto the core of capillary101-1. In one embodiment, the UV beamlet is focused such that its diameter decreases from about 1 millimeter at lens212/234to approximately 10 microns at the capillary core. In other embodiments, other optical focusing powers can be used. The desired spot size or beam diameter at capillaries101(and hence the needed focusing power) will depend in part on the diameter of a capillary101used for a particular implementation. In certain embodiments, one or more optical elements, such as one or more lenslets or diffractive optical elements (not shown), may be placed between fibers of fiber array251and the respective capillaries101to individually control the focus of one or more corresponding UV beamlets. Focusing of a UV beamlet to have a smaller beam diameter concentrates the power of the UV beamlet to the core of a capillary101. As a result, the accuracy of the UV absorption measurement is improved by reducing or eliminating cross talk between capillaries and by providing sufficient illumination power for obtaining usable transmittance or absorption measurements. The use of lenslet121therefore improves the signal-to-noise ratio for UV transmittance and absorption measurements.

As illustrated inFIG.3, UV beamlet mask131is disposed between lenslet121and capillary101-1. UV beamlet mask131can be, for example, a pinhole mask that reduces or eliminates UV lights or illuminations outside of the core of capillary101-1. UV beamlet mask131can thus further reduce cross talk between capillaries, and thus further improves the signal-to-noise ratio for UV transmittance and absorption measurements. Other lenslets and UV beamlet masks can be disposed in a similar manner as shown inFIG.3. The above description of UV beamlets coupling uses fiber251-1, lenslet121, mask131and capillary101-1as an example. It should be understood that other fibers, lenslets, masks, and capillaries can operate in a same or similar manner.FIG.3illustrates a short-working distance embodiment. In the illustrated embodiment, the lenslets have a short working distance and are disposed in close proximity (e.g., several microns to 1 mm) to the light outputting end of the respective fibers of fiber array251and to the respective UV beamlet masks and capillaries101. In some short-working distance embodiments, fiber array251, the short working-distance lenslet array, the UV beamlet masks, and the capillaries101are mounted relative to each other such that they are optically pre-aligned with one another. Further, in some embodiments of a short working-distance configuration as illustrated inFIG.3, fiber arrays251and261, the short working-distance lenslet array, the UV beamlet masks, and the capillaries101are integrated or packaged to a single replaceable assembly. When the capillaries need to be replaced, they are replaced by replacing the entire unit comprising the fiber arrays and the capillary array. Therefore, there is no need for the user to align the replaced capillary array with the fiber arrays because the fiber and capillary arrays are pre-aligned within the replacement unit.

In an alternative embodiment, illustrated inFIGS.7A and7B, pairs of prisms702are used to direct UV light for absorption measurements through each capillary in capillary array704. This arrangement allows capillary array704to be arranged parallel (rather than perpendicular) to receiving fiber array706and illuminating fiber array708. This can allow easier positioning of the capillary/fiber array unit inside the instrument.FIG.7Aillustrates a side view of this alternative andFIG.7Bshows a front view of a cross section of this alternative.FIG.7Bshows prism702and receiving fiber array706arranged above the capillary array704and prism702and illuminating fiber array708arranged below the capillary array704. Those skilled in the art would appreciate that as shown inFIG.7B, the receiving fiber array706includes a plurality of fibers, each of which is coupled with a respective prism702. Similarly, the illuminating fiber array708includes a plurality of fibers, each of which is coupled with a respective prism702. Also, each fiber in receiving fiber array706and each fiber in illuminating fiber array708are arranged with a corresponding capillary in capillary array704.

Returning to the description ofFIG.3, fiber array261receives the UV beamlets that pass through capillaries101. Fiber array261further delivers the received UV beamlets to detector module290(shown inFIG.2). In some embodiments, such as the embodiment illustrated inFIG.3, fibers in fiber array261preferably have larger diameters than those in fiber array251. For example, fiber261-1has a larger core diameter than that of fiber251-1. A larger diameter fiber in fiber array261improves collection efficiency associated with, for example, collecting UV beamlets that pass through capillaries101because of larger collection aperture. The delivering of the received UV beamlets and detection by a respective detector of detection module290are described in more detail below with respect toFIGS.4and5.

In an alternative embodiment (not shown inFIG.3), a long working-distance embodiment can be implemented. In such an embodiment, a fiber array (e.g., an illuminating fiber array similar to array251inFIG.3) directs UV beamlets to a long working-distance lenslet array, rather than a short working-distance lenslet array. A long working-distance lenslet array has a longer working distance (e.g., millimeters to centimeters), and therefore a longer focusing distance, than a short working-distance lens. In the alternative embodiment, long working-distance lenslets focus respective UV beamlets onto the cores of respective capillaries. Similar to those described above in the context ofFIG.3, UV beamlet masks can be disposed between the long working-distance lenslets and respective capillaries to reduce or eliminate UV lights or illuminations outside of the cores of the respective capillaries.

Further, the alternative embodiment also includes a receiving lenslet array disposed between the capillaries and a receiving fiber array. The receiving lenslet array can also be a long work-distance lenslet array. The receiving lenslet array receives the UV beamlets that pass through capillaries. The receiving lenslet array further focuses the received UV beamlets to respective fibers of the receiving fiber array. The receiving fiber array further delivers the received UV beamlets to detector module290(shown inFIG.2).

Unlike the short working-distance embodiment shown inFIG.3, a long working-distance embodiment enables the detachment of the lenslet arrays from the capillaries. As a result, the capillaries and lenslet arrays can be separately packaged and replaced. In a long working-distance fiber array based system, the capillaries are aligned to the lenslet arrays by an actuator. The actuator can be controlled by, for example, user device280. Further, because a long working-distance lenslet has a longer focusing distance than a short work-distance lenslet, a receiving long working-distance lenslet can better align and focus the UV beamlet received from a capillary to a corresponding receiving fiber. As a result, the receiving fibers are not required to have larger diameters than those in the illuminating fibers.

Beam b2: UV Fluorescence Measurement

With reference back toFIG.2, UV source202emits UV beam b2. In the illustrated embodiment, as previously described, UV source202may operate at a different wavelength than does UV sources201/204. As illustrated inFIG.2, half wave plate221and polarizing beam splitter222are configured to split beam b2into two beams: b2-R and b2-L. In one embodiment, beam b2is split evenly into beams b2-R and b2-L. In other embodiments, the splitting ratio can be adjusted to implement a non-even split.

Beam b2-R is reflected by mirror226through half wave plate253and is then reflected by mirrors227and228before passing through dichroic mirror247, and pinhole mask238. Lens248then focuses the beam onto or near capillaries101and the beam propagates through capillaries101in a first direction (right to left from the standpoint of the illustrations ofFIG.2).

Beam b2-L passes through half wave plate223, polarizing beam splitter231, half wave plate224, dichroic mirror244, and pinhole mask236. Lens225then focuses beam b2-L onto or near capillaries101and the beam propagates through capillaries101in a second direction, left to right from perspective of the illustration, opposite to that of the direction of b2-R. Splitting beam b2into beam portions b2-L and b2-R and propagating each beam portion through the array of capillaries101in opposite direction allows more even excitation energy to be provided across the array of capillaries101.

Fluorescence resulting from excitation of substances in each of the capillaries101by beams b2-L and b2-R is collected and collimated by fiber array261shown inFIG.2.FIG.3illustrates certain details regarding optical elements for collecting fluorescence. In some embodiments, fluorescence masks are disposed between capillaries101and respective fibers of fiber array261to reduce or eliminate fluorescence emission cross talk between adjacent capillaries. For example, fluorescence mask141is disposed between capillary101-1and fiber261-1to reduce or eliminate fluorescence emission cross talk between capillaries101-1and101-2. As illustrated, respective other fluorescence masks are similarly disposed (but not separately numbered) between respective other capillaries (101-2,101-3,101-4,101-5,101-6,101-7,101-8,101-ref) and fibers (261-2,261-2,261-3,261-4,261-5,261-6,261-7, and261-8, and261-ref).

As illustrated inFIG.3, using fluorescence mask141and/or the fluorescence mask disposed between capillary101-2and fiber261-2, fluorescence emissions from capillary101-1can be reduced or blocked such that fiber261-2receives substantially reduced or no fluorescence emissions from capillary101-1, and vice versa. The signal-to-noise ratio can therefore be improved. Fiber array261delivers the received fluorescence emissions to detector module290ofFIG.2. The delivering of the received fluorescence emissions and detection by a respective detector of detection module290are described in more detail below with respect toFIGS.4and5. In some embodiments, fibers in fiber array261may have larger diameters than those in fiber array251. For example, fiber261-1may have a larger core diameter than that of fiber251-1. A larger diameter fiber in fiber array261improves collection efficiency associated with, for example, collecting UV fluorescence emissions because of larger collection aperture.

Beam b3: Visible Fluorescence

As illustrated inFIG.2, visible light source203emits visible light beam b3. Half wave plate241and polarizing beam splitter242are configured to split beam b3into two beams: b3-R and b3-L. In one embodiment, beam b3is split evenly into beams b3-R and b3-L. In other embodiments, the splitting ratio can be adjusted to implement a non-even split.

Beam b3-R passes through half wave plate245and is reflected by mirror246and dichroic mirror247. Dichroic mirror reflects beam b3-R through pinhole mask238to lens248. Lens248then focuses the beam onto or near capillaries101and the beam propagates through capillaries101in a first direction (right to left from the standpoint of the illustrations ofFIG.2). Beam b3-L passes through half wave plate243and is reflected by dichroic mirror244through pinhole mask236to lens225. Lens225then focuses the beam onto or near capillaries101and the beam propagates through capillaries101in a second direction, left to right from perspective of the illustration, opposite to that of the direction of b3-R. Splitting beam b3into beam portions b3-L and b3-R and propagating each beam portion through the array of capillaries101in opposite direction allows excitation energy to be provided across the array of capillaries101more evenly.

Fluorescence resulting from excitation of substances in capillaries101by beams b3-L and b3-R is collected and collimated by fiber array261shown inFIG.2. As described above,FIG.3illustrates certain details regarding collecting fluorescence. Collecting fluorescence as a result of excitation from beam b3of visible light source203is the same or similar to that described above with respect to beam b2of UV source202, and thus is not separately described.

For fluorescent excitation beams originating from beams b2(UV) and b3(visible), pinholes (or beam masks)236and238can be used to block, respectively, the right-to-left propagating beams (b2-R and b3-R) and left-to-right propagating beams (b2-L and b3-L), as well as any back reflection from the capillary array resulting from those beams, from propagating back to sources202and203. Blocking of the counter-propagating beams and back reflections by pinholes236,238may be enhanced by use of an offset angle in the forward propagating beams.

Half wave plates224,253,243, and245can be used to rotate polarization of beams b2-L (plate224), b2-R (plate253), b3-L (plate243), and b3-R (plate245). The polarization rotations imparted by plates224and253(on UV beams b2-L and b2-R) can be used to control Raman background emission intensity and/or to reduce laser beam back reflection. The polarization rotations imparted by plates243and245(on visible light beams b3-L and b3-R) can be used for background controlling and/or reducing laser beam back reflection.

Dichroic mirrors244and247couple UV and visible light beams used for exciting fluorescence of substances in capillaries101. Specifically, dichroic mirror244coupled UV beam b2-L and visible light beam b3-L and dichroic mirror247couples UV beam b2-R and visible light beam b3-R.

Various Feature Combinations

The illustrated embodiment of optical detection system embodies various different combinations of features. These various combinations, alone or together, each form potentially distinct embodiments and the use of some combinations do not necessarily require use of the other combinations. For example:

In one aspect, optical detection system200provides optical pathways allowing two UV sources at different wavelengths to be used for absorption measurements. In another aspect, at least some of the optical components along the pathways corresponding to UV absorption measurements relying on each source are shared.

In another aspect, at least some optical components along a pathway for exciting fluorescence by a UV beam and along a pathway for exciting fluorescence by a visible light beam are shared and at least some components along pathways for collecting and measuring fluorescence of substances in capillaries excited by those beams are shared.

In a fully combined aspect, optical components are configured and arranged in optical detection system200to do the following: Measure UV absorption of substances in an array of capillaries using two UV sources operating a different wavelengths; excite and measure fluorescence of substances in the array of capillaries using one of the two UV sources; and excite and measure fluorescence of substances in the array of capillaries using a visible light source. In another aspect, one or more of the two UV sources and/or the visible light source are configured to provide a point source, for example, a laser and one or more optical element to produce a point source. In a related aspect, reference beams and a reference capillary are used to generate a reference signal for use in removing noise from measurement signals corresponding to the other capillaries.

FIG.4illustrates certain additional details regarding optical elements for parallel light detection in the optical detection system200ofFIG.2. The parallel light detection can be based on wavelength decoupling. As described above, fiber array261delivers UV beamlets that pass through capillaries101, fluorescence emission resulting from excitation by beam b2of UV source202, and/or fluorescence emission resulting from excitation by beam b3of visible light source203. These transmitted beamlets or emissions may be combined or mixed in fiber array261and delivered to detector module290. In some embodiments, detector module290can include different detectors for detecting light signals having different wavelengths for different types of measurements. For example, as illustrated inFIG.4, detector module290includes a detector291that detects image spots of transmitted UV beamlets (the UV beamlets that pass through capillaries101). Detector module290further includes a detector292that detects image spots of fluorescence emission resulting from excitation by beam b2of UV source202. Detector module290further includes a detector293that detects image spots of fluorescence emission resulting from excitation by beam b3of visible light source203.

As illustrated inFIG.4, optical detection system200can perform wavelength decoupling such that light signals having mixed wavelengths are imaged onto different detectors291-293. For example, to perform wavelength decoupling, optical detection system200can include a lenslet array401, dichroic mirrors421and422, a reflection mirror423, and lenslet arrays411,412, and413. Fiber array261transmits light signals having mixed wavelengths to lenslet array401. The lenslets in lenslet array401collimate the light signals received from fiber array261. In the embodiment shown inFIG.4, each lenslet in lenslet array401corresponds to a respective fiber in fiber array261.

The collimated light signals then propagate through dichroic mirror421, which is configured to separate light signals having a particular wavelength or wavelength band from the remaining light signals. For example, dichroic mirror421can separate, based on the wavelength differences, the UV beamlets that pass through capillaries101for transmittance/absorption measurements from the fluorescence emissions. Using dichroic mirror421, the UV beamlets having certain wavelength or wavelength band can pass through dichroic mirror421, but the fluorescence emissions having different wavelength or wavelength band are reflected. These UV beamlets that pass through dichroic mirror421then propagate further to fiber array441through lenslet array411. Lenslet array411focuses, collimates, and aligns the UV beamlets to fiber array441, which delivers the received UV beamlets to detector291. Detector291detects the image spots of these UV beamlets for UV transmittance and absorption measurements.

As illustrated inFIG.4, the fluorescence emissions reflected by dichroic mirror421propagate to dichroic mirror422, which is configured to separate light signals having a particular wavelength or wavelength band from the remaining light signals. For example, dichroic mirror422can separate, based on the wavelength differences, the fluorescence emissions resulting from excitation by beam b2of UV source202, and fluorescence emissions resulting from excitation by beam b3of visible light source203. Using dichroic mirror422, the fluorescence emissions resulting from excitation by beam b2of UV source202are reflected by dichroic mirror422, but the fluorescence emissions resulting from excitation by beam b3of visible light source203pass through dichroic mirror422. The UV fluorescence emissions that are reflected by dichroic mirror422then propagate further to fiber array442through lenslet array412. Lenslet array412focuses, collimates, and aligns these UV fluorescence emissions to fiber array442, which delivers the received UV fluorescence emissions to detector292. Detector292detects the image spots of these fluorescence emissions resulting from excitation by beam b2of UV source202for UV fluorescence measurements.

As described above, the fluorescence emissions that pass through dichroic mirror422can be fluorescence emissions resulting from excitation by beam b3of visible light source203. These fluorescence emissions can be reflected by mirror423and propagate further to fiber array443through lenslet array413. Lenslet array413focuses, collimates, and aligns these fluorescence emissions to fiber array443, which delivers the received fluorescence emissions to detector293. Detector293detects the image spots of these fluorescence emissions resulting from excitation by beam b3of visible light source203for visible light fluorescence measurements.

As illustrated inFIG.4and described above, using the dichromic mirrors and lenslet arrays, light signals with mixed wavelengths can be provided to respective detectors291,292, and293for performing different measurements (e.g., UV absorption, UV fluorescence, and visible fluorescence) simultaneously or at least partially in parallel. The ability to perform different measurements in parallel improves the measurement efficiency and speed.

FIGS.5A-5Cillustrate an alternative embodiment to the system portion illustrated inFIG.4. The embodiment shown inFIGS.5A-5Cis arranged for detecting different light serially rather than in parallel. Under certain circumstances, different measurements are performed in serial and thus light signals delivered by fiber array261may be for only one measurement type at a time. For example, the measurements for UV absorption, UV fluorescence, and visible fluorescence may be performed separately or one after another. As a result, at any given time, the light signals delivered by fiber array261may have a single wavelength or wavelength band. Wavelength decoupling as described above with respect toFIG.4may thus not be required.

In the embodiment illustrated inFIGS.5A-5C, fiber array261delivers light signals corresponding to a particular measurement type at a given time (UV absorption, UV fluorescence, or visible fluorescence). The light signals can include the UV transmitted (i.e., not absorbed) portion of beamlets from beams b1and b4that pass through capillaries101, fluorescence emission resulting from excitation by beam b2of UV source202, or fluorescence emission resulting from excitation by beam b3of visible light source203. Fiber array261delivers the light signals to fiber array541through coupling lenslet arrays501and511. Lenslet arrays501and511focus, collimate, and align light signals to fiber array541. In some embodiments, fiber array541includes a plurality of sub-arrays, each of which is optically coupled to a different detector. For example, fiber array541may include a fiber sub-array541-1optically coupled to detector291, a fiber sub-array541-2optically coupled to detector292, and a fiber sub-array541-3optically coupled to detector293. Fiber array541is sometimes referred to as a detector fiber array.

As illustrated in the side view ofFIG.5B, fiber array541can be mechanically attached to or mounted on a moveable stage (not shown). The moveable stage can be controlled (e.g., by user device280ofFIG.1) to align one sub-array of fiber array541with a respective detector291,292, or293and with coupling lenslet array511. For example, if UV transmittance or absorption measurement is being performed, fiber array261delivers the UV beamlets that pass through capillaries101. Moveable stage can be controlled to align fiber sub-array541-1to detector291and to the focal points of lenslet array511. Similarly, if UV fluorescence measurement is being performed, fiber array261delivers fluorescence emission resulting from excitation by beam b2of UV source202. Moveable stage can then be controlled to align fiber sub-array541-2to detector292and to the focal points of lenslet array511. And if visible light fluorescence measurement is being performed, fiber array261delivers fluorescence emission resulting from excitation by beam b3of visible light source203. Moveable stage can then be controlled to align fiber sub-array541-3to detector293and to the focal points of lenslet array511.

FIG.6Aillustrates another embodiment of the optical detection system of the embodiment ofFIG.1. In some embodiments, the UV sources and visible light sources shown inFIG.1may be lamps, instead of lasers. As illustrated inFIG.6A, additional optical elements can be used to couple light emitted from a lamp601to a fiber array251. Lamp601emits UV light or visible light. In contrast to a laser beam, the light emitted from lamp601is in a divergent shape such that the power of the emitted light is dispersed in a much greater angle than that of a laser beam. The emitted light from lamp601propagates to an illumination coupler, which include lens612and lens613. Lens612collects the emitted light from lamp601and lens613focuses the collected light onto fiber bundle650.

In one embodiment, as illustrated in the cross-sectional views shown inFIGS.6B and6C, fiber bundle650include a plurality of fibers arranged differently at different ends. The plurality of fibers is arranged in a bundle (e.g., fibers at least partially enclosed with a tube or a circular-shaped enclosure) at a first end650-in and arranged in a row or approximate straight line at a second end650-out. First end650-in receives light signals focused by lens613. Therefore, a more densely packed fiber bundle at first end650-in can have a higher optical coupling efficiency. Second end650-out and fiber array251are similarly arranged in a row or an approximate straight line. As a result, fiber bundle650can be optically aligned to couple to fiber array251for delivering light signals to capillaries101.

In some embodiments, lamp601may be a UV light source that emits light having more than one wavelength or wavelength bands. For example, lamp601may be a broadband UV light source that emits light having wavelengths corresponding to those of UV sources201,202, and204inFIG.1. At any given time, a particular measurement (e.g., an UV transmittance or absorption measurement) may be performed and may thus require using a light source having a particular wavelength or wavelength band. In some embodiments, a filter wheel614can be disposed between the illumination coupler (including lens612and lens613) and fiber bundle650. Filter wheel614can be controlled (e.g., by user device280) to select a proper filter to be disposed or inserted into the optical path between the illumination coupler and fiber bundle650. For example, when performing an UV transmittance or absorption measurement, a first filter of filter wheel614can be selected to allow UV lights having a first wavelength or wavelength band to pass, while substantially blocking lights having other wavelengths. Similarly, a second or a third filter of filter wheel614can be selected for performing UV fluorescence or visible light fluorescence measurements, respectively.

FIG.8is a block diagram illustrating signals output from detectors291,292, and293to DSP unit298and reduced noise signals output by DSP unit298. As will be appreciated, the separate lines shown from the detectors to DSP unit298and shown as output from DSP unit298do not necessarily represent distinct hardware connections between (and outputs from) the illustrated elements. Rather, they simply represent distinct signal channels. In some embodiments, these separate signal channels might be implemented with physically separate connections; however, in other embodiments, they are implemented as separate signal channels conveyed over the same physical conduit.

Each detector outputs nine signals to DSP unit298, i.e., one corresponding to each capillary measurement including measurement of eight capillaries comprising sample solutions and one reference capillary without any sample-filled solution. Detector291outputs to DSP298signals71-1,71-2,71-3,71-4,71-5,71-6,71-7,71-8, and71-ref, corresponding to first wavelength UV absorption measurements of, respectively, capillaries101-1,101-2,101-3,101-4,101-5,101-6,101-7,101-8, and101-ref. Signals71-1to71-8will include noise related to source201and/or source204, noise related to sample solutions, and noise related to the respective capillaries. Signal71-ref will contain the noise related to sources201/204and capillary101-ref, but it will not contain noise related to samples. DPS unit298removes noise related to the sources201/204and the capillaries from signals71-1to71-8by comparing them to reference signal71-ref using, for example, a cross correlation technique employing methods such as Weiner filtering, least squares filtering, and/or other techniques to obtain DSP output signals81-1,81-2,81-3,81-4,81-5,81-6,81-7. and81-8which have substantially reduced source and capillary related noise relative to signals71-1to71-8.

Detector292outputs to DSP298signals72-1,72-2,72-3,72-4,72-5,72-6,72-7,72-8, and72-ref, corresponding to second wavelength UV absorption measurements of, respectively, capillaries101-1,101-2,101-3,101-4,101-5,101-6,101-7,101-8, and101-ref. Signals72-1to72-8will include noise related to source202, noise related to sample solutions, and noise related to the respective capillaries. Signal72-ref will contain the noise related to source202and capillary101-ref, but it will not contain noise related to samples. DPS unit298removes noise related to the source and the capillaries from signals72-1to72-8by comparing them to reference signal72-ref using, for example, the previously described techniques for removing signal noise. DSP298outputs signals82-1,82-2,82-3,82-4,82-5,82-6,82-7. and82-8which have substantially reduced source and capillary related noise relative to signals72-1to72-8.

Detector293outputs to DSP298signals73-1,73-2,73-3,73-4,73-5,73-6,73-7,73-8, and73-ref, corresponding to UV fluorescence measurements of, respectively, capillaries101-1,101-2,101-3,101-4,101-5,101-6,101-7,101-8, and101-ref. Signals73-1to73-8will include noise related to source203, noise related to sample solutions, and noise related to the respective capillaries. Signal73-ref will contain the noise related to source203and capillary101-ref, but it will not contain noise related to samples. DPS unit298removes noise related to the source and the capillaries from signals73-1to73-8by comparing them to reference signal73-ref using, for example, the previously described techniques for removing signal noise. DSP298outputs signals83-1,83-2,83-3,83-4,83-5,83-6,83-7. and83-8which have substantially reduced source and capillary related noise relative to signals73-1to73-8.

DSP298can be implemented as processing logic in specifically configured hardware for example, in a Field Programmable Gate Array (FPGA) programmed for the relevant processing logic, in custom hardware, for example, in an Application Specific Integrated Circuit (ASIC), and/or in software executing on a special or general purpose processor (for example, on a processor of user device280, or on a processor located elsewhere in instrument1000).

While the present invention has been particularly described with respect to the illustrated embodiments, it will be appreciated that various alterations, modifications and adaptations may be made based on the present disclosure and are intended to be within the scope of the present invention.

Some examples of the many alternatives to the disclosed embodiments that could be implemented consistent with the spirit and scope of various aspects of the invention include, but are not limited, to the following: In some alternative embodiments, reflection rather than transmission optics (e.g., parabolic mirrors rather than lenses) can be used to direct the relevant beams onto the capillaries. In some embodiments, reflection rather than transmission optics could be used to direct the relevant beams onto the relevant detectors. In some embodiments, optical fibers could be used for the detection pathways (to direct light from the capillaries to the detectors) but not necessarily used for the illumination pathways (directing electromagnetic radiation from the source(s) to the capillaries).

In the illustrated embodiments, both transmittance/absorption measurements and fluorescent measurements are conducted based on illuminating the same window of a given capillary of the array. In other words, the same area of a capillary is targeted for illumination related to transmittance/absorption measurements and for illumination related to fluorescence measurements. However, in some alternative, separate windows could be used. For example, illumination for UV absorption measurements could occur at a first area of the capillary and illumination for fluorescence measurements could occur at a second area, longitudinally distant from the first area. In such embodiments, distinct optical paths would be implemented for each window and some of the separation optics of the embodiments illustrated inFIGS.2-6would not necessarily be needed.

These and other variations will be understood to be within the scope of the invention's potential embodiments.

While the invention has been described in connection with what are presently considered to be the most practical and preferred embodiments, it is to be understood that the present invention is not limited to the disclosed embodiments but, on the contrary, is intended to cover various modifications and equivalent arrangements included within the scope of the underlying principles of the invention as described by the various embodiments reference above and below.

Selected embodiments include:1. An optical detection system for a capillary electrophoresis instrument comprising:an ultraviolet (UV) source; andan absorption measurement optical path comprising a first plurality of optical elements arranged to obtain a plurality of respective UV beamlets from a UV beam emitted by the UV source and to direct the respective UV beamlets through respective capillaries of a plurality of capillaries and to an absorption detector positioned to detect respective signals for use in obtaining respective UV absorption measurements corresponding to the respective capillaries.2. The optical detection system of item 1 further comprising:a fluorescence excitation optical path comprising a second plurality of optical elements arranged to direct the UV beam though the plurality of capillaries and to direct respective fluorescence signals from the respective capillaries of the plurality of capillaries to a fluorescence detector positioned to detect the respective signals for use in obtaining respective fluorescence measurements corresponding to the respective capillaries.3. The optical detection system of item 2 wherein the second plurality of optical elements comprises at least some of the first plurality of optical elements.4. The optical detection system of item 2 wherein one or more optical elements of the first plurality of optical elements and the second plurality of optical elements are configurable to direct respective portions of the UV beam through the absorption measurement optical path and through the fluorescence measurement optical path substantially simultaneously.5. The optical detection system of item 2 wherein one or more optical elements of the first plurality of optical elements and the second plurality of optical elements are configurable to reconfigure the optical detection system between a first mode and a second mode, the first mode characterized by a configuration of the system in which the UV beam is directed on the absorption measurement optical path and the second mode characterized by a configuration of the system in which the UV beam is directed on the fluorescence measurement optical path.6. The optical detection system of item 1 wherein the UV source is a first UV source that operates at a first wavelength, the UV beam is a first UV beam, and the absorption measurement optical path is a first absorption measurement optical path, the optical detection system further comprising:a second UV source that operates at a second wavelength; anda second absorption measurement optical path comprising a third plurality of optical elements arranged to obtain a plurality of respective UV beamlets from a UV beam emitted by the second UV source and to direct the respective UV beamlets through respective capillaries of a plurality of capillaries and to an absorption detector positioned to detect respective signals for use in obtaining respective UV absorption measurements corresponding to the respective capillaries.7. The optical detection system of any one of items 1-6 further comprising:a visible light source;a fluorescence excitation optical path comprising a third plurality of optical elements arranged to direct a fluorescence excitation light beam from the visible light source though the plurality of capillaries and to direct respective fluorescence signals from the respective capillaries of the plurality of capillaries to a visible light fluorescence detector positioned to detect the respective signals for use in obtaining respective fluorescence measurements corresponding to the respective capillaries.8. The optical detection system of any one of items 1-5 wherein the UV source is a point source; or of item 6 wherein the UV source is a point source and the second UV source is a point source; or of item 7 wherein the UV source is a point course, the second UV source is a point source, and the visible light source is a point source.9. The optical detection system of item 8 wherein one of the respective capillaries is designated as a reference capillary, the optical detection system further comprising:a digital signal processing unit configured to use signals corresponding to the reference capillary to remove UV source and capillary signal noise from signals corresponding to other capillaries of the respective capillaries wherein the other capillaries are designated to carry samples.10. The optical detection system of item 1 wherein the first plurality of optical elements comprise a diffractive optical element used to obtain the respective UV beamlets from the UV beam.11. An optical detection system for a capillary electrophoresis instrument comprising:a first ultraviolet (UV) source that operates at a first wavelength;a first absorption measurement optical path comprising a first plurality of optical elements arranged to obtain a plurality of first respective UV beamlets from a UV beam emitted by the first UV source and to direct the respective UV beamlets through respective capillaries of a plurality of capillaries and to an absorption detector positioned to detect respective signals for use in obtaining respective UV absorption measurements corresponding to the respective capillaries;a second UV source that operates at a second wavelength; anda second absorption measurement optical path comprising a second plurality of optical elements arranged to obtain a plurality of second respective UV beamlets from a UV beam emitted by the second UV source and to direct the second respective UV beamlets through respective capillaries of the plurality of capillaries and to an absorption detector positioned to detect respective signals for use in obtaining respective UV absorption measurements corresponding to the respective capillaries.12. The optical detection system of item 11 wherein the second plurality of optical elements comprises at least some of the first plurality of optical elements.13. The optical detection system of item 11 further comprising:a fluorescence excitation optical path comprising a third plurality of optical elements arranged to direct a UV beam originated from the first UV source though the plurality of capillaries and to direct respective fluorescence signals from the respective capillaries of the plurality of capillaries to a fluorescence detector positioned to detect the respective signals for use in obtaining respective fluorescence measurements corresponding to the respective capillaries.14. The optical detection system of item 13 wherein the third plurality of optical elements comprises at least some of the first plurality of optical elements.15. The optical detection system of any one of items 11-14 further comprising:a visible light source;a fluorescence excitation optical path comprising a fourth plurality of optical elements arranged to direct a fluorescence excitation light beam from the visible light source though the plurality of capillaries and to direct respective fluorescence signals from the respective capillaries of the plurality of capillaries to a visible light fluorescence detector positioned to detect the respective signals for use in obtaining respective fluorescence measurements corresponding to the respective capillaries.16. The optical detection system of item 15 wherein the fourth plurality of optical elements comprises at least some of the third plurality of optical elements.17. The optical detection system of any one of items 11-14 wherein the first UV source and the second UV source are point sources; or of any one of items 15-16 wherein the first UV source is a point source, the second UV source is a point source, and the visible light source is a point source.18. The optical detection system of item 17 wherein one of the respective capillaries is designated as a reference capillary, the optical detection system further comprising:a digital signal processing unit configured to use signals corresponding to the reference capillary to remove UV source and capillary signal noise from signals corresponding to other capillaries of the respective capillaries wherein the other capillaries are designated to carry samples.19. The optical detection system of item 11 wherein the first plurality of optical elements comprises a diffractive optical element used to obtain the first respective UV beamlets from the first UV beam.20. An optical detection system for a capillary electrophoresis instrument comprising:an ultraviolet (UV) point source;an absorption measurement optical path comprising a first plurality of optical elements arranged to obtain a plurality of respective UV beamlets from a UV beam emitted by the UV point source and to direct the respective UV beamlets through respective capillaries of a plurality of capillaries and to an absorption detector positioned to detect respective signals for use in obtaining respective UV absorption measurements corresponding to the respective capillaries.21. The optical detection system of item 20 further comprising:a fluorescence excitation optical path comprising a second plurality of optical elements arranged to direct the UV beam though the plurality of capillaries and to direct respective fluorescence signals from the respective capillaries of the plurality of capillaries to a fluorescence detector positioned to detect the respective signals for use in obtaining respective fluorescence measurements corresponding to the respective capillaries.22. The optical detection system of item 21 wherein the second plurality of optical elements comprises at least some of the first plurality of optical elements.23. The optical detection system of item 21 wherein one or more optical elements of the first plurality of optical elements and the second plurality of optical elements are configurable to direct respective portions of the UV beam through the absorption measurement optical path and through the fluorescence measurement optical path substantially simultaneously.24. The optical detection system of item 21 wherein one or more optical elements of the first plurality of optical elements and the second plurality of optical elements are configurable to reconfigure the optical detection system between a first mode and a second mode, the first mode characterized by a configuration of the system in which the UV beam is directed on the absorption measurement optical path and the second mode characterized by a configuration of the system in which the UV beam is directed on the fluorescence measurement optical path.25. The optical detection system of item 20 wherein the UV source is a first UV source that operates at a first wavelength, the UV beam is a first UV beam, and the absorption measurement optical path is a first absorption measurement optical path, the optical detection system further comprising:a second UV source that is a point source and that operates at a second wavelength; anda second absorption measurement optical path comprising a third plurality of optical elements arranged to obtain a plurality of respective UV beamlets from a UV beam emitted by the second UV source and to direct the respective UV beamlets through respective capillaries of a plurality of capillaries and to an absorption detector positioned to detect respective signals for use in obtaining respective UV absorption measurements corresponding to the respective capillaries.26. The optical detection system of any one of items 20-25 further comprisinga visible light point source;a fluorescence excitation optical path comprising a second plurality of optical elements arranged to direct a fluorescence excitation light beam from the visible light point source though the plurality of capillaries and to direct respective fluorescence signals from the respective capillaries of the plurality of capillaries to a visible light fluorescence detector positioned to detect the respective signals for use in obtaining respective fluorescence measurements corresponding to the respective capillaries.27. The optical detection system of any one of items 20-25 further comprising:a digital signal processing unit configured to use signals corresponding to a reference capillary of the respective capillaries to remove UV source and capillary signal noise from signals corresponding to other capillaries of the respective capillaries wherein the other capillaries are designated to carry samples.28. The optical detection system of any one of items 20-24, wherein the point source produces a beam having a beam diameter that is less than or equal to 5 micrometers, less than or equal to 10 micrometers, less than or equal to 20 micrometers, less than or equal to 50 micrometers, less than or equal to 100 micrometers, or less than or equal to 200 micrometers.29. The optical detection system of item 20 wherein the first plurality of optical elements comprise a diffractive optical element used to obtain the respective UV beamlets from the UV beam.30. An optical detection system for a capillary electrophoresis instrument comprising:an ultraviolet (UV) source; andan absorption measurement optical path comprising a first plurality of optical elements comprising a first optical fiber array and other elements, the first plurality of optical elements being arranged to:obtain a plurality of respective UV beamlets from a UV beam emitted by the UV source, anddirect, at least partially using the first optical fiber array, the respective UV beamlets through respective capillaries of a plurality of capillaries and to an absorption detector positioned to detect respective signals for use in obtaining respective UV absorption measurements corresponding to the respective capillaries.31. The optical detection system of item 30, wherein the first plurality of optical elements further comprises:a lenslet array comprising respective lenslets, the respective lenslets being arranged to align the respective UV beamlets directed using the first optical fiber array to the cores of the respective capillaries of the plurality of capillaries; anda plurality of respective UV beamlet masks disposed between the respective lenslets of the lenslet array and the respective capillaries of the plurality of capillaries, the respective UV beamlet masks being arranged to reduce UV light illuminations from the respective UV beamlets outside of the cores of the respective capillaries of the plurality of capillaries.32. The optical detection system of item 30, wherein the UV source is a first UV source that operates at a first wavelength, the UV beam is a first UV beam, and the absorption measurement optical path is a first absorption measurement optical path, the optical detection system further comprising:a second UV source that operates at a second wavelength; anda second absorption measurement optical path comprising a second plurality of optical elements comprising the first optical fiber array and other elements, the second plurality of optical elements being arranged to:obtain a plurality of respective second UV beamlets from a second UV beam emitted by the second UV source, anddirect, at least partially using the first optical fiber array, the respective second UV beamlets through the respective capillaries of the plurality of capillaries and to the absorption detector.33. The optical detection system of item 30, wherein the UV source is a first UV source that operates at a first wavelength, the UV beam is a first UV beam, the optical detection system further comprising:a third UV source; anda UV fluorescence excitation optical path comprising a third plurality of optical elements arranged to direct a third UV beam emitted from the third UV source through the plurality of capillaries and to direct respective fluorescence signals from the respective capillaries of the plurality of capillaries to a UV fluorescence detector positioned to detect the respective signals for use in obtaining respective UV fluorescence measurements corresponding to the respective capillaries.34. The optical detection system of item 33, wherein the first plurality of optical elements and the third plurality of optical elements are configurable to concurrently direct the first UV beam and the third UV beam through the absorption measurement optical path and through the UV fluorescence measurement optical path, respectively.35. The optical detection system of item 33, further comprising:a visible light source;a visible fluorescence excitation optical path comprising a fourth plurality of optical elements arranged to direct a visible fluorescence excitation light beam emitted by the visible light source though the plurality of capillaries and to direct respective visible fluorescence signals from the respective capillaries of the plurality of capillaries to a visible light fluorescence detector positioned to detect the respective signals for use in obtaining respective visible fluorescence measurements corresponding to the respective capillaries.36. The optical detection system of item 35, wherein the first plurality of optical elements, the third plurality of optical elements, and the fourth plurality of optical elements are configurable to concurrently direct the first UV beam, the third UV beam, and the visible fluorescence excitation light beam, respectively, through the absorption measurement optical path, through the UV fluorescence measurement optical path, and through the visible fluorescence excitation optical path, respectively.37. The optical detection system of item 36, wherein the first plurality of optical elements, the third plurality of optical elements, and the fourth plurality of optical elements comprise a same second optical fiber array arranged to deliver one or more of:the UV beamlets that pass through the plurality of capillaries;UV fluorescence emission resulting from excitation by the third UV beam; and visible fluorescence emission resulting from the visible fluorescence excitation light beam.38. The optical detection system of item 37, wherein the second optical fiber array is optically coupled to a plurality of wavelength decoupling elements arranged to direct, concurrently, at least two of:the UV beamlets that pass through the plurality of capillaries to the absorption detector,the UV fluorescence emission resulting from excitation by the third UV beam to the fluorescence detector, and the visible fluorescence emission resulting from the visible fluorescence excitation light beam to the visible light fluorescence detector.39. The optical detection system of item 37, wherein the second optical fiber array is optically coupled, separately in time, to one of:a third optical fiber array arranged to direct the UV beamlets that pass through the plurality of capillaries to the absorption detector;a fourth optical fiber array arranged to direct the UV fluorescence emission resulting from excitation by the third UV beam to the fluorescence detector, or a fifth optical fiber array arranged to direct the UV fluorescence emission resulting from excitation by the third UV beam to the fluorescence detector.40. The optical detection system of item 30, wherein the UV source is a light source that emits lights having a plurality of wavelengths, further comprising a wavelength selecting element arranged to select a wavelength or wavelength range comprising a subset of the plurality of wavelengths.41. The optical detection system of item 40 wherein the wavelength selecting element comprises a filter wheel.