Capillary electrophoretic device employing structure permitting electrical contact through ionic movement

Abstract

A capillary tube has a structure in its wall that permits ions to flow but no substantial amount of electrolyte to move therethrough. The structure therefore permits electrical contact between the electrolyte inside the tube and the outside environment without diluting the electrolyte. The structure forms only a small part of the side wall so that the tube retains its structural integrity and can be used in electrophoresis without requiring structural support. In the preferred embodiment, the structure is formed by drilling a hole in the side wall, filling the hole with glass powder and fused silica and heating the mixture to form a frit structure to plug the hole. The frit structure permits ions to flow but substantially no electrolyte to move therethrough. Electrophoretic samples exiting from the end of the tube are not diluted and can be continuously collected, such as on top of a moving plate.

What is claimed is: 
     
       1. A capillary tube .Iadd.having an inlet hole and an outlet hole, .Iaddend.comprising: a wall .[.surrounding an axis.]. .Iadd.extending between the inlet hole and the outlet hole.Iaddend., said wall defining a first space inside the wall and a second space outside the wall, said wall suitable for containing and confining an .[.electrolytic solution.]. .Iadd.electrolyte in the first space.Iadd., said outlet hole permitting a solution to flow through it.Iaddend.; and   .[.a.]. .Iadd.at least one frit .Iaddend.structure in the wall extending between the first and second spaces .[.said structure not completely surrounding the axis so that the wall retains its structural integrity and so that the tube is suitable for use in electrophoresis without requiring structural support,.]. .Iadd.and between the inlet and the outlet holes.Iaddend., wherein said structure permits ions .Iadd.to pass .Iaddend.but substantially no .[.electrolytic.]. solution to flow therethrough, so that said structure permits electrical contact between the first and second spaces through ionic movement. .[.2. The tube of   
     
     
        claim 1, wherein said structure is a frit structure..]. 3. The tube of claim .[.2.]. .Iadd.1.Iaddend., wherein the .Iadd.at least one .Iaddend.frit structure is created by making a hole in one side of the tube, inserting an object into the first space to block one end of the hole, filling at least a portion of the hole with a glass powder and heating the powder at a temperature close to the sintering temperature of 
     
     
        the glass powder. 4. The tube of claim .[.2.]. .Iadd.1, .Iaddend.wherein said .Iadd.at least one .Iaddend.frit structure is composed of fused 
     
     
        silica and solder glass. 5. A capillary electrophoretic device comprising: a tube having an inlet and an outlet .[.end.]., .Iadd.said tube being unbranched between the inlet and the outlet, .Iaddend.said tube including:   (a) a wall .[.surrounding an axis, said wall.]. defining a first space inside the wall and a second space outside the wall, said wall suitable for containing and confining an .[.electrolytic solution.]. .Iadd.electrolyte .Iaddend.and electrophoretic sample in the first space;   (b) a structure in the wall extending between the first and second spaces, .[.said structure not completely surrounding the axis so that the wall retains its structural integrity and so that the tube is suitable for use in electrophoresis without requiring structural support,.]. wherein said structure permits ions .Iadd.to pass .Iaddend.but substantially no .[.electrolytic.]. solution to flow therethrough, so that said structure permits electrical contact between the first and second spaces through ionic movement; and   means for applying an electrical potential .[.between.]. .Iadd.across .Iaddend.the electrolyte and sample .[.at.]. .Iadd.between .Iaddend.the inlet .[.end.]. of the tube and the .[.electrolyte and the sample at the.]. structure .Iadd.so that the inlet and the structure are at different electrical potentials, said structure located between the inlet and the outlet of the tube so that the electrical potential applied by the applying means causes the sample in the first space to flow out of the   
     
     
        outlet.Iaddend.. 6. The device of claim 5, said electrical potential applying means comprising a first reservoir in contact with said inlet .[.end.]. of the tube and a second reservoir in contact with the structure, said first and second reservoirs being at different electrical 
     
     
        potentials. 7. The device of claim 5, .Iadd.wherein said electrolyte is a solution, and .Iaddend.wherein the electrical potential applied by the applying means causes .[.an.]. .Iadd.the .Iaddend.electrolyte in the first space to flow from the inlet .[.end.]. toward the outlet .[.end.]., said device further comprising a detector placed adjacent to or inside the tube at a point between the structure and the outlet .[.end.]. for detecting the electrolyte at an electrical potential substantially equal to the 
     
     
        electrical potential of the structure. 8. The device of claim 5, .Iadd.wherein said electrolyte is a solution, and .Iaddend.wherein the electrical potential applied by the applying means causes .[.an.]. .Iadd.the .Iaddend.electrolyte in the first space to flow from the inlet .[.end.]. towards the outlet .[.end.]., said device further comprising means for collecting samples of the electrolyte that flows from the tube 
     
     
        at the outlet .[.end.].. 9. The device of claim 5, wherein said structure 
     
     
        is a frit structure. 10. The tube of claim 9, wherein said frit structure is composed of fused silica and solder glass. .[.11. A method of making a capillary tube with a frit structure for use in electrophoresis comprising: making a hole at one side of a capillary tube;   inserting a body inside the tube to block the hole from a position inside the tube;   filling at least a portion of the hole with glass powder;   heating a portion of the tube surrounding the hole and the glass powder to a temperature at or near the sintering temperature of the glass powder so that the powder forms the frit structure; and   withdrawing the body from the tube..]. .[.12. The method of claim 11, wherein the making step comprises directing a laser beam at said one side   
     
     
        of the capillary tube..]. 13. An electrophoretic method employing a capillary tube having .[.a first.]. .Iadd.an inlet .Iaddend.and .[.a.]. .Iadd.an .Iaddend.outlet .[.end.]., .Iadd.said tube being unbranched between the inlet and the outlet, .Iaddend.said tube including: (i) a wall .[.surrounding an axis, said wall.]. defining a first space inside the wall and a second space outside the wall, said wall suitable for containing and confining an .[.electrolytic solution.]. .Iadd.electrolyte .Iaddend.in the first space; (ii) a structure in the wall extending between the first and second spaces .[.said structure not completely surrounding the axis so that the wall retains its structural integrity and so that the tube is suitable for use in electrophoresis without requiring structural support,.]. .Iadd.and located between the inlet and the outlet.Iaddend., wherein said structure permits ions .Iadd.to pass .Iaddend.but substantially no .[.electrolytic.]. solution to flow therethrough, so that said structure permits electrical contact between the first and second spaces through ionic movement; said method comprising: introducing an electrolyte and a sample into the tube;   applying a voltage across the sample and electrolyte .[.at.]. .Iadd.between .Iaddend.the inlet .[.end.]. of the tube and the .[.electrolyte and sample at the.]. structure so that the .[.electrolyte and sample flow from the inlet end toward the outlet end.]. .Iadd.inlet and the structure are at different electrical potentials, thereby causing the sample to separate into its components and flow out from the outlet.Iaddend.; and   collecting the effluent from the outlet .[.end.]. so that the sample   
     
     
        components separated in the electrophoresis process remain separate. 14. The method of claim 13, wherein the collecting step causes relative motion between the outlet .[.end.]. and a surface and deposits the effluent onto the surface in order to record the effluent output as a 
     
     
        function of time. 15. The method of claim 14, wherein the collecting step 
     
     
        moves the surface. 16. The method of claim 14, wherein the collecting steps moves the outlet .[.end.].. .Iadd.17. A method for electrophoretic separation comprising the steps of: providing a capillary tube having an inlet and an exit, said capillary having no side branch between the inlet and the exit, said capillary containing a sample and electrolyte;   applying an electrical potential across the electrolyte and sample in a section of the capillary tube to cause electrophoretic separation of the sample into its components; wherein the electrical potential applied causes the separated components to flow out of the exit of the capillary tube; and   collecting and maintaining said separated components in a separated state. .Iaddend. .Iadd.18. A method as in claim 17 wherein the collecting and maintaining step comprises the steps of:   positioning a collection device in flow communication with the exit of the capillary tube; and   distributing the separated components spatially on the collection device. .Iaddend. .Iadd.19. A method as in claim 18 wherein the distributing step comprises the step of causing relative motion between a collection device and the exit of the capillary tube such that the separated components are spatially distributed and remain separated. .Iaddend. .Iadd.20. A method as in claim 19 wherein the collection device is a continuous surface. .Iaddend. .Iadd.21. A method as in claim 20 wherein the step of applying electrical potential comprises the step of providing at least one structure along the capillary tube near the exit, wherein said structure allows ionic contact with the electrolyte from outside the tube. .Iaddend. .Iadd.22. A method as in claim 21 further comprising the step of providing a detector for detecting the presence of the separated components migrating in the capillary tube. .Iaddend. .Iadd.23. A method as in claim 22 wherein the detector is provided at a location between the structure and the exit of the capillary tube. .Iaddend. .Iadd.24. A system for electrophoretic separation comprising:   a capillary tube having an inlet and an exit, said capillary tube having no side branch between the inlet and exit, the capillary containing a sample and electrolyte;   means for applying an electric potential across the electrolyte and sample in a section of the capillary tube to cause electrophoretic separation of the sample into its components;   means for causing the separated components to flow out of the exit of the capillary tube; and   means for collecting and maintaining said separated components in a separated state. .Iaddend. .Iadd.25. A system as in claim 24 wherein the collecting and maintaining means comprises:   a collection means positioned in flow communication with the exit of the capillary tube; and   means for distributing the separated components spatially on the collection means. .Iaddend. .Iadd.26. A system as in claim 25 wherein the means for distributing causes relative motion between the collection means and the exit of the capillary tube such that the separated components are distributed and remain separated. .Iaddend. .Iadd.27. A system as in claim 26 wherein the collection means is a continuous surface. .Iaddend. .Iadd.28. A system as in claim 27 wherein the applying means comprises at least one structure along the capillary tube near the exit which allows ionic contact with the electrolyte from outside the tube. .Iaddend. .Iadd.29. A system as in claim 28 wherein the causing means applies an electric potential across the section of the capillary tube. .Iaddend. .Iadd.30. A system as in claim 29 further comprising a detector for detecting the presence of the separated components in the capillary tube. .Iaddend. .Iadd.31. A system as in claim 30 wherein the detector is positioned at a location between the structure and the exit of the capillary tube. .Iaddend. .Iadd.32. The device of claim 5, wherein the electrical potential applied by the applying means causes the electrolyte and sample in the first space to flow from the inlet toward the outlet, said device further comprising a detector placed adjacent to or inside the tube at a point between the structure and the outlet for detecting the sample at an electrical potential substantially equal to the electrical potential of the structure. .Iaddend. .Iadd.33. The device of claim 5, wherein said wall surrounds an axis, said structure not completely surrounding the axis so that the wall retains its structural integrity and so that the tube is suitable for use in electrophoresis without requiring structural support. .Iaddend. .Iadd.34. The device of claim 5, wherein the electrical potential applied by the applying means causes the electrolyte and sample in the first space to flow from the inlet towards the outlet, said device further comprising a collector device collecting the sample that flows from the tube at the outlet. .Iaddend. .Iadd.35. The capillary tube of claim 1, wherein said first space has cross sectional dimensions of the order of 75 microns. .Iaddend.