Abstract:
An optical fiber ( 500 ) illuminates the bore ( 520 ) of a capillary tube ( 515 ) that is used for separating chemicals by capillary electrophoresis (CE). The fiber terminates in either two sloped regions ( 525 ) and a curved region ( 530 ) or two sloped regions ( 705 ) and a flat region ( 700 ). Light from these regions is focused on the bore of the capillary tube. Since the fiber is sized to illuminate the core of a CE capillary, it is larger than fibers used in telecommunications and its sloped regions are at angles that would be unsuitable for use in telecommunications. The relatively large diameter of the capillary permits efficient use of a light source ( 905 ).

Description:
BACKGROUND 
     Prior Art—Elecrophoresis—FIGS.  1 - 4   
     Electrophoresis is a powerful and well-known method that is used in many fields of science to separate molecules having different sizes and different intrinsic electrical charges in order to analyze and synthesize chemical compounds. It is used in DNA sequencing, in the separation of mixtures of proteins, and the like. Two principal methods for performing electrophoretic separations are in routine use today. 
     Planar Gel Matrix: 
     The first method uses a planar gel matrix, such as agarose, with electrodes located at opposite edges of the gel. A mixture of ionized, i.e., charged, molecules is applied near the electrode on one edge of the gel, and an electrical potential is applied to the electrodes. Because of their intrinsic electrical charge the molecules are urged to move away from one electrode and toward the other one. The motion of the charged molecules is impeded by the structure of the molecules within the gel. The speed at which the charged molecules move depends upon their size, i.e., smaller molecules having a particular electrical charge move faster through the gel than larger ones with the same charge. Thus the difference in speeds results in separation of the previously mixed molecules. In most cases the various molecular species are not normally visible to the human eye. Prior to separation they are combined with dye molecules or tagged with radioactive atoms in well-known fashion, thus rendering them visible either by direct visual inspection or through the exposure of photographic film, respectively. Analysis of this separation is used to quantify the size and numbers of molecules contained in the original mixture. 
     Capillary Electrophoresis: 
     The second method, capillary electrophoresis (CE), is used by analytical chemists to separate ionic species from mixtures of chemical compounds. Instead of the planar arrangement described above, CE employs a narrow tube (capillary) through which the molecules move as they are separated. 
       FIGS. 1 and 2  are schematic drawings of a prior-art apparatus for performing a CE separation and an on-capillary detection. On-capillary means the point at which the separation is detected is in a section of the tube or capillary that is used in the actual separation, i.e., there is no interruption from the separation conduit to the detection cell. The apparatus comprises a capillary tube  100 , a source of electrical potential  105 , an anode  110 , and a cathode  115 . Cathode  115  and anode  110  are respectively connected to source  105  by electrical conductors  135  and  130 . A light source  120  and a detector  125  are arranged so as to shine light through tube  100 . Tube  100  is filled with a matrix substance such as a buffer solution  140 , i.e., one that resists changes in pH when small quantities of a base or acid are added to it. The ends of capillary tube  100  are inserted into solutions contained in vials or other containers  116 ,  117 , and  118 . Capillary tube  100  is typically made of glass or quartz and has a bore (internal diameter) ranging between 50 and 100 microns, an outer diameter of 200-360 microns, and a length of 20 to 50 cm, although other sizes are used. 
       FIG. 1  shows the apparatus being loaded with a sample mixture  145  of an ionic species, such as biological molecules, having an intrinsic electrical charge. In this case, the intrinsic electrical charge of the molecules is positive so that they will move away from anode  110  toward cathode  115  as they are separated. If the intrinsic molecular charge is known to be negative, the electrical source polarity would be reversed, or the sample can be introduced at the cathode. The right-hand end of capillary  100  and cathode  115  are immersed in a buffer solution  140  in vial  118 . 
     To load sample  145 , electrical source  105  and light source  120  are de-energized. Vial  116  containing a solution of sample  145  to be separated is positioned so that anode  110  and the left-hand end of capillary  100  are immersed in sample solution  145 . A small amount of the sample is urged into capillary  100  either using hydrostatic pressure or a brief application of electrical potential from source  105 , in well-known fashion. After introduction of the sample, vial  116  is removed and replaced with vial  117  ( FIG. 2 ) so that, prior to separation, the sample forms a band in a uniform matrix. 
       FIG. 2  shows the prior-art apparatus of  FIG. 1  in use. Electrical source  105  and light source  120  are energized. Detector  125 , such as a photodiode or photomultiplier tube, is connected to a computer  200  or other data recorder. The electric field established between anode  110  and cathode  115  within matrix  140  in capillary tube  100  urges the molecular components comprising sample  145  ( FIG. 1 ) to move toward the cathode. As explained above, the smaller molecules move faster within matrix  140  and are thus separated from the slower-moving larger molecules. Light source  120  and detector  125  are located near cathode  115  since separation of the molecular species will be greatest at that location. Light source  120  emits a predetermined wavelength or band or bands of wavelengths of light of known intensity. Light from source  120  is arranged to shine through matrix  140  in capillary tube  100  and then onto detector  125 . When illuminated, the molecules in sample  145  either absorb or absorb and re-emit light that is captured by detector  125 . Intensities of the incident light from source  120  and the light reaching detector  125  are compared and recorded in computer  200  for later analysis. Sample concentration is calculated using a well-known formula, the Beer-Lambert law, explained, e.g., under “Beer-Lambert Law” in the Internet encyclopedia Wikipedia. 
     Light from source  120  that falls on matrix  140  within capillary  100  must be as bright as possible in order to maximize detection sensitivity of the apparatus. Thus source  120  is a critical part of this apparatus. Its intensity determines the dynamic range over which the apparatus operates. With higher intensity, greater the signal-to-noise ratio and linearity can be achieved in measurements. 
     The following is a list of some possibly relevant prior art that shows such light sources. Following this list I provide a discussion of these references. 
     
       
         
               
             
               
               
               
               
             
           
               
                   
               
               
                 U.S. Patents 
               
             
          
           
               
                   
                   
                 Issue 
                   
               
               
                 Patent or Pub. Nr. 
                 Kind Code 
                 or Pub. Date 
                 Patentee or Applicant 
               
               
                   
               
               
                 3,910,677 
                 A1 
                 Oct. 07, 1975 
                 Becker et al. 
               
               
                 5,037,199 
                 A1 
                 Aug. 06, 1991 
                 Hlousek 
               
               
                 5,239,360 
                 A1 
                 Aug. 24, 1993 
                 Moring et al. 
               
               
                 5,455,879 
                 A1 
                 Oct. 03, 1995 
                 Modavis et al. 
               
               
                 5,845,024 
                 A1 
                 Dec. 01, 1998 
                 Tsushima et al. 
               
               
                 6,317,550 
                 B2 
                 Nov. 13, 2001 
                 Irie et al. 
               
               
                 6,597,835 
                 B2 
                 Jul. 22, 2003 
                 Jie et al. 
               
               
                   
               
             
          
         
       
     
     Non-Patent Literature 
     
         
         Bruno, A. E. et al., “Theoretical considerations on the design of cylindrical flow cells utilizing optical fibres”, Analytica Chimica Acta, 234 (1990) 259-262.
 
References that Show Light Input to an Optical Fiber from a Source Such as a Laser
 
       
    
     Becker shows a hyperbolic type optical fiber lens coupler that couples an optical fiber to an optical line source such as a laser diode. A cylindrical lens is used at the input end of an optical fiber in order to increase light collection and thereby coupling efficiency. The lens has a curved (hyperbolic) middle portion and two slanted side portions. Although Becker does not state a core diameter, he does state that his system is used in communications systems. For telecommunications applications, a single-mode optical fiber is required, in which the core diameter must be 10 microns or less. 
     Modavis shows a wedge-shaped, anamorphic micro-lens with two pairs of slanted surfaces formed at the end of a single-mode optical fiber that collects light from a laser. Modavis&#39;s mode field width, i.e. the effective width of light propagation in his fiber, is about 2 microns; the core width would be somewhat less. 
     Tsushima shows a manufacturing process for making tapered elliptic and cylindrical lenses for coupling to light sources such as laser diodes and light-emitting diodes. Tsushima&#39;s core diameter is about 6 microns. 
     Irie shows a wedged lens at the end of an optical fiber for coupling to a laser beam. The lens has a plane portion  2   d , perpendicular to the axis of the fiber, in the middle of the fiber and two symmetrical slant portions on the sides of the fiber. Irie&#39;s plane portion has a width of 1, 2, 4, or 6 microns or μm as indicated in Irie&#39;s  FIG. 3 . 
     Jie shows a wedged lens at the end of an optical fiber having a substantially flat portion formed at the end of the fiber core, two slant portions formed at the end of the fiber cladding, and curved portions between the flat and slanted portions. Jie&#39;s core diameter is 6 microns. 
     The small core diameter of the fibers used in these references is optimal for each of their purposes, i.e. the single-mode light propagation. However, the small core diameters severely limit the amount of light that can be emitted from one end of the fiber even if the other end of the fiber were illuminated by the brightest of sources. 
     References that Show Light Output from an Optical Fiber that is Used to Illuminate a Capillary Tube 
     Hlousek and Moring both show the use of a ball lens to focus light on the inner channel of a capillary. Although the use of a ball lens increases light intensity within the capillary, the spherical aberration associated with a ball lens compromises the linear range of detection available in such a system. 
     Bruno shows the use of a flat-end optical fiber to illuminate a capillary, with no focusing lens between them. Although simple, the absence of a lens significantly reduces the amount of light that can be applied to the sample through the small fiber, because the size of the fiber must be smaller than the inner capillary channel. As a result, the signal-to-noise ratio of this apparatus is compromised. 
     The above-described references are each useful for their intended purposes. However each has one or more disadvantages as noted. 
     SUMMARY 
     I have discovered a new method for illuminating the capillary cores in an on-capillary CE apparatus. The need for a ball lens is eliminated, the light output is improved over that supplied by a flat-ended fiber, and a larger fiber with a different end configuration than those for use in telecommunications is used. In various aspects, the light-emitting end of an optical fiber is formed into predetermined shapes that permit a moderately-sized light source to properly illuminate the core of a CE capillary. 
    
    
     
       DRAWING FIGURES 
         FIGS. 1 and 2  show a prior art CE system. 
         FIGS. 3 and 4  show two prior-art light collecting fibers. 
         FIGS. 5 ,  6 , and  6 A show side, end, and perspective outline views, respectively, of one aspect of an embodiment. 
         FIGS. 7 ,  8 , and  8 A show side, end, and perspective outline views, respectively, of a different aspect of the embodiment of  FIGS. 5-6A . 
         FIG. 9  shows a perspective view of one aspect of an on-capillary absorbance detector apparatus incorporating the embodiments shown in  FIGS. 5 through 8A . 
     
    
    
     
       
         
               
             
               
               
               
               
             
           
               
                   
               
               
                 DRAWING REFERENCE NUMERALS 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 100 
                 Capillary tube 
                 105 
                 Electrical source 
               
               
                 110 
                 Anode 
                 115 
                 Cathode 
               
               
                 120 
                 Light source 
                 125 
                 Detector 
               
               
                 130 
                 Conductor 
                 135 
                 Conductor 
               
               
                 140 
                 Matrix 
                 145 
                 Sample 
               
               
                 200 
                 Computer 
                 300 
                 Optical fiber 
               
               
                 305 
                 Cladding layer 
                 310 
                 Core 
               
               
                 315 
                 Slope 
                 500 
                 Optical fiber 
               
               
                 505 
                 Core 
                 510 
                 Cladding 
               
               
                 515 
                 Capillary 
                 520 
                 Bore 
               
               
                 525 
                 Sloped region 
                 530 
                 Convex region 
               
               
                 700 
                 Flat region 
                 705 
                 Flat region 
               
               
                 900 
                 Absorbance detector apparatus 
                 905 
                 Light source 
               
               
                 909 
                 Terminal 
                 910 
                 Block 
               
               
                 915 
                 Tube 
                 920 
                 Cover 
               
               
                 925 
                 Photodetector housing 
                 930 
                 Platform 
               
               
                 935 
                 Epoxy 
                 940 
                 Channel 
               
               
                 945 
                 Bore 
                 950 
                 V-Groove 
               
               
                   
               
             
          
         
       
     
     DESCRIPTION 
     Brief Discussion of Prior Art for Illuminating Fibers—FIGS.  3  and  4   
       FIGS. 3 and 4  show two optical fibers that are formed according to Becker and Irie, supra, respectively. These two are representative of the remaining light collecting references. These references show variations in the means for coupling light from a source, such as a laser or light-emitting diode (LED), into an optical fiber. In all cases, the ends of the fibers are ground, polished, and formed to various geometries. 
       FIG. 3  shows a cylindrical lensed optical fiber  300  of Becker comprising an outer cladding layer  305  and an inner core  310 , and having a circular cross-section. Core  310  is ground to a “substantially hyperbolic cylinder type optical coupling surface”, while cladding layer  305  is ground to a slope  315  at a predetermined angle θ with respect to the axis of optical fiber  300 . 
       FIG. 4  shows the cylindrical lensed optical fiber  300 ′ of Irie comprising an outer cladding layer  305 ′ and an inner core  310 ′. In this case, the end of optical fiber  300 ′ is ground to a taper or slope  315 ′ at an angle θ′ and core  310 ′ extends a predetermined distance outside cladding  305 ′. The remaining references show variations on the theme of grinding and polishing the ends of optical fibers for use as light collectors from lasers and LEDs. 
     DESCRIPTION 
     First Aspect of Embodiment—FIGS.  5  and  6   
       FIGS. 5 through 8A  show two aspects of an optical fiber for illuminating a portion of the core of a CE capillary according to a first embodiment.  FIGS. 5 ,  6 , and  6 A show a first aspect, specifically side, front, and perspective outline views of a round cylindrical optical fiber  500  that has a central core  505  and cladding  510 . The boundary between core  505  and cladding  510  is indicated by dashed lines. The right end of fiber  500  comprises a lens or lensed region with a rectangular convex end or region  530  ( FIG. 6A ) and two generally triangular sloped regions  525  and  525 ′ which extend back from region  530 . As shown in  FIG. 6A , regions  525 ,  525 ′, and  530  are discrete and each faces in a different direction. 
     A CE capillary tube  515  ( FIG. 5 ) with an inner bore  520  is positioned a predetermined distance D from optical fiber  500 . The axis of tube  515  (including its bore  520 ) is oriented perpendicular to optical fiber  500  as shown. The diameter of core  505  of optical fiber  500  is typically 100-200 microns and is much larger than the diameter of bore  520  of capillary  515 , which typically is 50-100 microns, although other sizes can be used. 
     In the aspect shown in  FIGS. 5-6A , and as shown in  FIG. 9 , the light emitted from the end of optical fiber  500  is focused on a part of capillary  515  between the ends thereof. Fiber  500  is formed into three regions: a convex region  530  with radius r, and two sloped flat regions  525  and  525 ′ that are formed at an angle α and are symmetrical to the axis of fiber  500 . As shown best in  FIGS. 5 and 7 , regions  525  and  525 ′ are sloped or slanted with respect to the axis of fiber  500  and the perpendicular line to such axis. I.e., regions  525  and  525 ′, being sloped or slanted, lie between but not at 0 and 90 degrees to the axis of fiber  500  and the perpendicular to axis  500 . The extent of convex region  530  between flat regions  525  and  525 ′ is approximately the same as the diameter of bore  520  of capillary  515 , typically 50-100 microns, although values ranging from 0.5 to 2 times the diameter of bore  520  can be used. The radius of curvature r is selected to place the focal point of convex region  530  at the central axis of bore  520  of capillary  515 . Thus radius r is determined by the predetermined distance D between optical fiber  500  and capillary  515 . Angle α is also selected to place the light ray from the middle of sloped flat regions  525  and  525 ′ within or very near to the center of bore  520  of capillary  515 . Typically, radius r is 100-150 microns and angle α is 20-30 deg., although other dimensions can be used. If angle α is greater than 42°, total internal reflection will occur within optical fiber  500  and this will reduce the amount of light leaving optical fiber  500 . Light from a source such as  905  ( FIG. 9 ) entering the left-hand end of fiber  500  is indicated by arrows  535 . Focused light leaving the right-hand end of fiber  500  and passing through capillary  515  is identified by a plurality of rays E, F, G, and H. 
     Second Aspect of First Embodiment—FIGS.  7  and  8   
       FIGS. 7-8A  show side, end, and perspective outline views, respectively, of a second, alternative aspect which is similar to that of  FIGS. 5-6A  but in which the end of optical fiber  500 ′ that is focused on capillary tube  515  is formed into three flat regions. A first flat region  700  is located between second and third flat regions  705  and  705 ′, respectively, and extends between regions  705  and  705 ′ a distance equal or smaller than the diameter of bore  520  of capillary  515 , although a range of thicknesses from 0.5 to 2 times the diameter of bore  520  can be used. Second and third flat regions  705  and  705 ′, respectively, traverse core  505 ′ and cladding  510 ′ and are both ground at an angle α′, symmetrical to the axis of core  500 ′. As in the previous aspect, angle α′ is selected to place the light ray from the middle of sloped flat regions  705  and  705 ′ of optical fiber  500 ′ within or very near to bore  520  of capillary  515 . If angle α′ is greater than 42 deg, total internal reflection within optical fiber  500 ′ will reduce the amount of light leaving optical fiber  500 ′. Light entering the left-hand end of fiber  500 ′ is indicated by arrows  535 . Focused light leaving the right-hand end of fiber  500 ′ and passing through capillary  515  is identified by a plurality of rays E′, F′, G′, and H′. 
     In the aspects shown in  FIGS. 5 through 8A , the angles α and α′ are typically 20-30 degrees and cannot go beyond 42 degrees, while in the prior art fiber optics discussed above the slope angles, converted to α and α′ for comparison, lie typically between 40 and 50 degrees. In addition, the present optical fiber has a core diameter of 100-200 microns, while the prior-art fibers have core diameters of 10 microns or less. 
     Flat surfaces  525 ,  700 , and  705  and curved surface  530  are ground using an abrasive wheel (not shown) or other similar arrangement. Methods for forming these surfaces are discussed in the cited prior art, such as Becker, Modavis, and Jie, and will not be discussed further here. 
     Capillary  515  and optical fiber  500  are made of glass or quartz, although other materials including plastics can be used. Light  535  can be white light comprising many wavelengths, or it can contain only one or a few selected wavelengths ranging from ultraviolet through the visible to infrared. Sources for this light can be light-emitting diodes, gaseous discharge tubes, arc lamps, incandescent lamps, plasma discharges, and the like. Sources with a range of wavelengths can be filtered to deliver one or a few wavelengths, if required. The material from which capillary  515  and optical fiber  500  are made is selected to pass, i.e., not attenuate, the wavelength of light in use. In some cases light  535  of one wavelength is used to stimulate fluorescence of a second wavelength within the sample in bore  520  of capillary  515 . The materials from which capillary  515  and optical fiber  500  are made are well-known and take these considerations into account. 
     Operation 
     First Embodiment—FIG.  9   
       FIG. 9  shows an exploded perspective view of one aspect of the above embodiments in use. An exemplary absorbance detector apparatus  900  comprises a light source  905  and optical fibers  500 ″. One or more fibers is used, generally less than four. The fibers extend through a block  910  which connects to a tube  915 , both of which form a terminal  909 . A cover  920  is fitted over terminal  909  and all of the foregoing elements are positioned on one side of capillary  515  as stated. A photodetector housing  925  is positioned on the other side of capillary  515 . Absorbance detector apparatus  900  (other than the light source and optical fibers) is opaque and made of metal, plastic, or wood. 
     Tube  915  terminates at its left-hand end in block  910 . At the right-hand end of tube  915  is a platform  930  to which one or more of optical fibers  500 ″ are secured by a layer of epoxy  935 . Optical fibers  500 ″ are secured within block  910  and are then secured to light source  905 . Optical fibers  500  are all oriented perpendicularly to bore  520  of capillary  515  as shown in  FIGS. 5 and 7 . 
     Cover  920  has an open channel  940  at its left-hand end and a central bore  945 . A pair of V-grooves  950  are formed into the right-hand end of cover  920  across its diameter. Block  910  and tube  915  are sized to slidably fit into cover  920 . V-grooves  950  are sized to mate with capillary  515 . Capillary  515  is fixedly seated in grooves  950  (not shown) when photodetector housing  925  is urged against the right-hand end of cover  920  and secured there in well-known fashion, usually by screws or a clamp arrangement. Two grooves are used since capillary  515  is normally flexible and must be supported on both sides of bore  945 . 
     Terminal  909  is then fully inserted into cover  920 . End  530  of optical fiber  500  ( FIG. 5 ) or end  700  of optical fiber  500 ′ ( FIG. 7 ) is thus held at a predetermined distance from capillary  515  to ensure that distance D or D′ ( FIGS. 5 and 7 ), respectively, is maintained. Thus when absorbance detector apparatus  900  is fully assembled, optical fibers  500  are secured at the proper distance from capillary  515 . 
     Once assembled, absorbance detector apparatus  900  can be firmly secured by a clamp (not shown) or other means. 
     The assembly of terminal  909  and cover  920  thus position, align, and maintain the proper distance between the end of optical fiber  500  (or  500 ′) and capillary  515 . 
     CONCLUSIONS, RAMIFICATIONS, AND SCOPE 
     I have provided an improved lensed optical fiber for use in on-capillary detection apparatus. My design is an improvement over a flat-ended fiber and it does not require a separate lens, such as a ball lens, to properly direct light into the bore of a CE capillary for use in evaluating electrophoretic separations. Because the end of my optical fiber is shaped into a lens, a large core fiber can be used to efficiently illuminate a capillary without an additional lens. 
     While the above description contains many specificities, these should not be construed as limitations on the scope, but as exemplifications of some present embodiments. Many other ramifications and variations are possible within the teachings herein. For example, optical fibers made of a variety of formulations of plastic, glass, and quartz can be used. The optical fibers can have predetermined colors and they can range in length from a few millimeters to many meters. In absorbance detector apparatus  900 , various changes can be made, such as eliminating open channel  940  and using a manual alignment and bond, and making block  910  and platform  930  perpendicular. My lensed optical fiber can also be used to quantify liquid chromatographic separations performed within translucent capillaries. 
     Thus the scope should be determined by the appended claims and their legal equivalents, rather than the examples and particulars given.