Electrospray emitter module for capillary electrophoresis device

Abstract

A capillary emitter includes a coupling sleeve, a separation capillary inside the coupling sleeve, the separation capillary extending along a longitudinal axis of the coupling sleeve, a tip at an end of the coupling sleeve, the tip comprising an orifice and having an internal base, a first hollow internal cavity defined on one side thereof by the internal base in the coupling sleeve, the first hollow internal cavity comprising the separation capillary, and a fluid pathway within the first hollow internal cavity, the fluid pathway surrounding the separation capillary, wherein, at the internal base of the tip, the separation capillary and the fluid pathway are fluidly connected within the first hollow internal cavity.

Description

[0001] ELECTROSPRAY EMITTER MODULE FOR CAPILLARY ELECTROPHORESIS DEVICE

[0002] Cross-Reference To Related Application

[0003] This application is being filed as a PCT International application and claims the benefit of and priority to U.S. Provisional Application No. 63 / 514,836, filed July 21, 2023, the disclosure of which is hereby incorporated by reference in its entirety.

[0004] Background

[0005] Capillary electrophoresis (CE) devices include a tip from which an ionic sample is projected to, e.g., a mass spectrometer, while the CE device is subjected to a voltage. Typically , the lip deteriorates when high voltages are applied thereto.

[0006] Summary

[0007] In one aspect, the technology relates to a capillary emitter including a coupling sleeve, a separation capillary inside the coupling sleeve, the separation capillary extending along a longitudinal axis of the coupling sleeve, a tip at an end of the coupling sleeve, the tip including an orifice and having an internal base, a first hollow internal cavity defined on one side thereof by the internal base in the coupling sleeve, the first hollow internal cavity including the separation capillary, and a fluid pathway within the first hollow internal cavity, the fluid pathway surrounding the separation capillary, wherein, at the internal base of the tip, the separation capillary and the fluid pathway are fluidly connected within the first hollow internal cavity.

[0008] In another example of the above aspect, an inside diameter of the orifice of the tip is in a range of 20 pm to 75 pm. In another example, the inside diameter of the orifice of the tip is equal to about 30 pm. In a further example, an outside diameter of the tip is in a range of 40 pm to 100 pm. In another example, the outside diameter of the tip is equal to about 60 pm. In yet a further example, an internal diameter of the separation capillary is equal to the inside diameter of the orifice of the tip. In yet another example, a material of the tip includes a non-conductive material. In a further example, a material of the tip includes a refractory oxide. For example, the refractory oxide includes a ceramic. In another example, the refractory oxide includes at least one of zirconium oxide, titanium carbonitride, alumina, and titanium nitride. In another example, the internal base of the tip has a substantially flat profile. In a further example, the internal base of the tip is substantially perpendicular to the longitudinal axis of the separation capillary. In a further example, the separation capillary abuts the internal base of the tip inside the first hollow internal cavity.

[0009] In another example of the above aspect, the capillary emitter is configured to be joined to a separation capillary holder, and a second hollow internal cavity inside the capillary emitter encompasses a portion of the separation capillary holder, the second hollow internal cavity being larger than the first hollow internal cavity. In a further example, the second hollow internal cavity and the portion of the separation capillary holder form a watertight seal. In yet another example, the second hollow internal cavity and the portion of the separation capillary holder are held together via an adhesive. For example, the second hollow internal cavity and the portion of the separation capillary holder are held together via a sleeve. In another example, an outside diameter of the separation capillary is in a range of 100 pm to 360 pm. For example, the outside diameter of the separation capillary is equal to about 150 pm. In yet another example, the internal base of the tip and the separation capillary define a clearance therebetween. In a further example, the clearance is in a range of about 1 pm to about 20 pm. For example, the clearance is equal to about 10 pm. In another example, the internal base of the tip and the opening of the tip form an inlet comer at an intersection thereof, the inlet comer having a rounded profile.

[0010] In another aspect, the technology relates to a capillary assembly including a housing, the capillary emitter as discussed above, wherein a first portion of the separation capillary of the capillary emitter is inserted in a separation capillary holder, and a second portion of the separation capillary of the capillary emitter is inserted in a first lumen, a conducting fluid capillary inserted in a second lumen parallel to the first lumen, a conductive fitting around the separation capillary holder along a longitudinal direction thereof, and a compression fitting around the separation capillary holder, the compression fitting being adjacent to the conductive fitting along the longitudinal direction of the separation capillary holder.

[0011] In an example of the above aspect, the first lumen is a central lumen and the second lumen is radially around the first lumen. In another example, the capillary assembly further includes a third lumen configured to flow a coolant therethrough, the third lumen being parallel to the first lumen and the second lumen. In a further example, the separation capillary is coupled to a sample source outside of the housing, and the conducting fluid capillary is coupled to a conducting fluid source outside of the housing. In yet another example, the capillary assembly further includes a tip cover encompassing an exit end of the separation capillary, a rigid fitting encompassing the separation capillary holder, and a nozzle in fluid communication with the tip cover via a port formed in the conductive fitting and via a space formed between the separation capillary holder and the rigid fitting. In a further example, the nozzle is configured to introduce a nebulizing gas to the tip cover via the space. In a further example, the tip cover is configured to mix the nebulizing gas with a liquid sample emitted from the capillary emitter. In yet another example, the capillary assembly further includes a fourth lumen configured to flow a substance therethrough, the fourth lumen being parallel to the first lumen, the second lumen and the third lumen.

[0012] Brief Description of the Drawings

[0013] FIG. 1 is a schematic view of a ceramic tip for a capillary emitter in an electrospray ionization (ESI) assembly, in accordance with various examples of the disclosure.

[0014] FIGS. 2A-2B is a cross-section and an enlarged cross-section, respectively, of a capillary emitter for an ESI assembly, in accordance with various examples of the disclosure.

[0015] FIGS. 3A-3B is a cross-section and an enlarged cross-section, respectively, of a capillary' emitter tip for an ESI, in accordance with various examples of the disclosure.

[0016] FIG. 4 is a table illustrating the evolution of signal noise with respect to ESI voltage for a capillary emitter in an ESI assembly, in accordance with various examples of the disclosure.

[0017] FIGS. 5A-5B are a cross-section and an enlarged cross-section, respectively, of a capillary' emiter tip for an ESI assembly with a nebulizer assembly, in accordance with various examples of the disclosure. Detailed Description

[0018] Examples of this disclosure relate to a capi llary emitter of a CE device having a capillary emitter tip that can sustain high voltages without substantially deteriorating. For low flow CE applications coupled to, e.g., a mass spectrometer, the emitter tip preferably allows for the return of the CE separation current and a potential for the ionization to the inlet of the mass spectrometer. As further discussed below with respect to FIG. 4, higher ESI voltages may at times be desired to reduce signal noise and achieve high signal-to-noise ratios, and it is advantageous that emitter tips used in such systems are able to sustain high voltages without suffering significant damage, or without suffering significant damage in a too short period of time. Current CE applications typically use an etched tip to permit current flow through fissures in a 5- pm capillary wall after etching. These tips are typically difficult to produce and are very fragile. Their performance can vary and is not always consistent. Examples of this disclosure use a robust tip design that produces equivalent or better results when compared to the current etched tip design. Such tips, e.g., ceramic tips, can be mass produced at a substantial cost improvement over the typical processes which include etching a capillary with, e.g., hydrofluoric acid, and handling the tip with great precision and care after etching. A ceramic or refractive oxide tip being non- conductive and having a sharp point with an orifice equal to the inner diameter of the separation capillary to which it is coupled can produce similar low flow electrospray performance to the current etched capillary.

[0019] As further discussed with respect to FIGS. 1-5 below, the separation capillary may be abutted to the inner wall of the ceramic tip to reduce dead volume and to provide a deliberately imperfect seal between the inner wall of the ceramic tip and the separation capillary so as to allow a conductive fluid to pass around the end of the separation capillary and establish an electrical connection with the liquid in the separation capillary. The electrical connection in turn allows the application of any desired ionization voltage to generate ions that are then transferred to, e.g., a mass spectrometer, from the tip of the separation capillary. Accordingly, the fluid from the tip of the separation capillary to the conductive fitting establishes the electrical connection. During operation of the CE device, the electric voltage may be applied to the fluid passing through the orifice of the ceramic tip instead of on the tip itself because the tip is non-conductive. Accordingly, higher ESI voltages may be sustained without substantial damage to the separation capillary tip, which may result in lower noise in the resulting signal and increase longevity of the separation capillary.

[0020] FIG. 1 is a schematic view of a tip for a capillary emitter in an ESI assembly, in accordance with various examples of the disclosure. The tip may be, e.g., a ceramic tip or a refractive oxide tip. In FIG. 1, the capillary emitter 100 includes a separation capillary 110 that may be coupled to a CE device (not shown). An outside diameter of the separation capillary 110 may be in a range of 100 pm to 360 pm, and may be, e.g., equal to about 150 pm. The separation capillary 110 may be inserted in a double lumen 120 that includes a first lumen and a second lumen, and may be configured to transport a liquid sample through, e.g., the first lumen. A conductive fluid capillary 130 may be inserted in the second lumen of the double lumen 120, the first lumen and the second lumen being parallel to each other so that the conductive fluid capillary 130 is parallel with the separation capillary 110. For example, the separation capillary 110 may extend in the first lumen along a central axis of the double lumen 120, and the conductive fluid capillary 130 may extend in the second lumen off-center from the central axis of the double lumen 120. The double lumen 120 may provide a seal against the outside diameter of the separation capillary 110 and the conductive fluid capillary 130.

[0021] The conductive fluid capillary 130 may be configured to transport a conductive fluid therethrough such as, e.g., a conductive liquid. On an opposite side of the separation capillary from the CE device, the capillary emitter 100 includes a tip 140. A material of the tip 140 may be, e.g., a refractory oxide, and the refractory oxide may be, e.g., a ceramic. In examples, the refractory oxide may be or include any combination of zirconium oxide, titanium carbonitride, alumina, and titanium nitride. At about a middle portion of the capillary emitter 100, the separation capillary 110 is surrounded by one or compression fittings 150 such as, e.g., two (2) compression fittings 150. The capillary emitter 100 may further include a conductive fitting 160, also along a middle portion of the capillary emitter 100, that surrounds the separation capillary 110. The conductive fitting 160 may be, e.g., between two (2) compression fittings 150. In examples, the combination of the conductive fitting 160 and the compression fittings may form together a housing.

[0022] FIGS. 2A-2B are cross-sections of a capillary emitter 100 for an ESI assembly, in accordance with various examples of the disclosure. FIG. 2A illustrates the capillary emitter 100 having the double lumen 120 in which the separation capillary 110 and the conductive fluid capillary 130 are inserted. The conductive fitting 160, which surrounds a portion of the double lumen 120, has a triangular cross-section with an apex at about a middle portion of the separation capillary 110, and is book-ended by the two compression fittings 150. The cross-sections of the compression fittings 150 are such that a portion of each compression fitting 150 is inserted in a corresponding concave portion of the conductive fitting 160. FIG. 2A also illustrates a non-conductive tube or separation capillary holder 170 that extends from the double lumen 120 along a longitudinal axis of the separation capillary 110 to the tip portion 190. The separation capillary holder 170 encompasses the separation capillary 110 along a length thereto but does not encompass the conductive fluid capillary 130. The conductive fluid capillary 130, inside the double lumen 120, extends up to the point of separation between the double lumen 120 and the separation capillary holder 170. Accordingly, the conductive fluid present inside the conductive fluid capillary 130 transfers inside the separation capillary holder 170 so that the conductive fluid is inside an inner diameter of the separation capillary holder 170 and around or outside the separation capillary 110. The conductive fluid may thus flow from the conductive fluid capillary 130 to a space between the separation capillary 110 and the inner diameter of the separation capillary holder 170 up to the end portion 190 of the capillary emitter 100.

[0023] The separation capillary holder 170 may be provided, e.g., to provide structural support to the separation capillary 110 and void or reduce the risk of breakage of the separation capillary 110 particularly given the length thereof. On a side of the separation capillary holder 170 opposite to the double lumen 120, the capillary emitter 100 includes a coupling sleeve 180 that includes the end portion 190, and the end portion 190 is further discussed below with respect to FIG. 2B. At the interface between the coupling sleeve 180, the conductive fluid that is inside the inner diameter of the separation capillary holder 170 flows through an inner space generated by the inside diameter of the coupling sleeve 180 and the separation capillary 110 which extends up to the end portion 190, as discussed in greater detail below with respect to FIG. 2B.

[0024] FIG. 2B illustrates the end portion 190 of the capillary emitter 100, in accordance with various examples of the disclosure. In FIG. 2B, the end portion 190 includes a portion of the coupling sleeve 180, the coupling sleeve including therein the separation capillary 110 along a longitudinal axis thereof, the separation capillary 110 being surrounded by the conductive fluid flowing from the inner diameter of the coupling sleeve 180. Due to the existence of a deliberately imperfect seal between the inner wall of the coupling sleeve 180 and the separation capillary 110 at a side face 185 of the separation capillary 110, the conductive fluid is allowed to pass around the end of the separation capillary 110 and establish an electrical connection with the liquid therein. An electrical connection may thus be formed between the liquid sample inside the separation capillary 110 and the conductive fluid inside the coupling sleeve 180. Accordingly, an ionization voltage may be applied to the liquid sample inside the separation capillary 110 due to electrical connection thus formed. In operation, the conductive fluid may flow between the separation capillary 110 and the inner diameter of the coupling sleeve 180, and then out through orifice or opening 195 in the tip 140 of the end portion 190, the tip 140 being the tip of the coupling sleeve 180, or integrally formed with the coupling sleeve 180. Thus, when a voltage is applied, the liquid sample inside the separation capillary 110 may be ionized, and the ions may be ejected from the orifice 195 to, e.g., the mass spectrometer. With respect to the orifice 195 of the tip 140 of the coupling sleeve 180, an inside diameter thereof may be in a range of about 20 pm to about 75 pm, or may be, e.g., equal to about 30 pm. In other examples, the outside diameter of the tip 140 may be in a range of about 40 pm to about 100 pm, or may be, e.g., equal to about 60 pm. In addition, the internal diameter of the separation capillary 110 may be substantially equal to the inside diameter of the orifice 195.

[0025] In FIG. 2B, the separation capillary 110 abuts an inner wall 182 of the coupling sleeve 180, also referred to herein as the internal base 182 of the coupling sleeve 180. Although the internal base 182 is referred to herein as being the internal base 182 of the coupling sleeve 180, the internal base 182 may also be referred to as the internal base of the tip 140 due to the location thereof at the interface between the tip 140 of the coupling sleeve 180 and the main body of the coupling sleeve 180. For example, the internal base 182 may correspond to the inside bottom wall of the tip 140. The internal base 182 may have a substantially flat profile, or may be substantially perpendicular to the longitudinal axis of the separation capillary 110. The internal base 182 and the separation capillary 110 may also define a clearance therebetween that may be in a range of about 1 pm to about 20 pm, or may be e.g., equal to about 10 pm. The internal base 182 and the orifice 195 may also form an inlet comer at an intersection thereof, the inlet comer having a rounded profile to facilitate ejection of the ionized liquid sample to, e.g., the mass spectrometer.

[0026] FIGS. 3A and 3B illustrate a capillary emitter tip for a capillary emitter, in accordance with various examples of the disclosure. In FIG. 3A, the separation capillary holder 170, which provides structural support to the separation capillary 110, extends along a longitudinal axis of the separation capillary 110 and encompasses a portion of the separation capillary. FIG. 3 A also illustrates the coupling sleeve 180 that encompasses both the separation capillary holder 170 and the portion of the separation capillary 110 that is not encompassed by the separation capillary holder 170. The coupling sleeve 180 may define a hollow internal cavity 184 therein, also referred to as a first hollow internal cavity 184. The first hollow internal cavity 184 may include the portion of the separation capillary 110 that is not encompassed by the separation capillary holder 170 therein. In examples, the separation capillary holder 170 does not extend up to the tip 140 of the coupling sleeve 180, which leaves a space 188 inside the inner diameter of the coupling sleeve 180, and the conductive liquid that flows between the inner diameter of the separation capillary holder 170 and the separation capillary 110 may flow in the space 188 inside the coupling sleeve 180 and around or outside the separation capillary 110. As illustrated in greater detail in FIG. 3B, a fluid pathway may thus be created between the side face 185 of the separation capillary 110, the inner space inside the coupling sleeve 180, and the orifice 195 of the tip 140 of the coupling sleeve 180, the fluid pathway surrounding the separation capillary 110 such that, at the internal base 182, the separation capillary 110 and the fluid pathway are fluidly connected within the first hollow internal cavity 184 by the conductive liquid, which allows the application of an ionization voltage to the liquid inside the separation capillary 110.

[0027] In various examples, the coupling sleeve 180 of the capillary emitter 100 is configured to be joined to the separation capillary holder 170, and includes a second hollow internal cavity 186 that encompasses a portion of the separation capillary holder 170. For example, the second hollow internal cavity 186 may be larger than the first hollow internal cavity 184. The second hollow internal cavity 186 and the portion of the separation capillary holder 170 that is encompassed thereby may form a watertight seal. In examples, the second hollow internal cavity 186 and the portion of the separation capillary holder 170 may be held together via an adhesive, or the second hollow internal cavity 186 and the portion of the separation capillary holder 170 may also be held together via a sleeve such as, e.g., the coupling sleeve 180.

[0028] FIG. 4 is a table illustrating the evolution of noise for the signal detected at the mass spectrometer with respect to ESI voltage applied to the tip of a capillary emitter, in accordance with various examples of the disclosure. In FIG. 4, Table 400 illustrates the noise percentage (%) and the coefficient of variation percentage (CV %), which is the standard deviation of the signal divided by the mean over the entire range of ESI voltages, with respect to the applied voltage. Table 400 clearly shows that higher applied ESI voltages result in lower noise percentages and coefficients of variation percentages. Accordingly, having capillary emitters, such as the capillary emitters 100 discussed above and 500 discussed below, that can sustain high ESI voltages, can provide appreciable advantages.

[0029] FIGS. 5A-5B are schematic views of a capillary emitter tip for an ESI assembly with a nebulizer assembly, in accordance with various examples of the disclosure. In FIG. 5A, the assembly 500 has a housing 505 that houses a separation capillary 510 and a conductive fluid capillary 530. The separation capillary 510 may be coupled, at an opposite end thereof from the assembly 500, to a sample source outside of the housing 505, and may be inserted in the first lumen of a double lumen 520. The separation capillary 510 may be configured to transport a liquid sample therethrough, the liquid sample being the liquid sample to be analyzed, e.g., via a mass spectrometer. The conducting fluid capillary 530 may be inserted in the second lumen of the double lumen 520, and may be coupled to a conducting fluid source outside of the housing 505. The conductive fluid capillary 530 may be inserted in the double lumen 520 in parallel with the separation capillary 510. The conductive fluid capillary 530 may be configured to transport a conductive fluid therethrough such as, e.g., a conductive liquid, and the second lumen of the double lumen 520 may be off-center from the longitudinal axis of the double lumen 520, while the separation capillary 510 may be disposed along a central axis of the double lumen 520. On an end portion of the separation capillary 510, the assembly 500 includes a tip portion 540 that includes a tip 542 such as, e.g., a ceramic ESI tip 542. At about a middle portion of the assembly 500, the double lumen 520, in which both the separation capillary 510 and the conductive fluid capillary 530 are inserted, is housed within a compression fitting 550. The assembly 500 may further include a conductive fitting 560, also along a middle portion of the assembly 500, that surrounds the double lumen 520. FIG. 5A also illustrates a non-conductive tube or separation capillary holder 570 that extends from the double lumen 520 along a longitudinal axis of the separation capillary 510 and that encompasses a portion of the separation capillary 510 but does not encompass the conductive fluid capillary 530. The conductive fluid that is within the conductive fluid capillary 530 flows from the conductive fluid capillary 530 through an inner diameter of the separation capillary holder 570 and around the separation capillary 510. Thus, the conductive fluid may flow between the separation capillary 510 and an inner diameter of the separation capillary holder 570 from the end of the double lumen 520 up to the tip portion 540.

[0030] The assembly 500 also includes a conductive tube 575 that encompasses the separation capillary holder 570 and that extends from the end of the double lumen 520 up to the tip portion 540. The conductive tube 575 may also be referred to as rigid fitting 575. FIG. 5A further illustrates a gas or fluid port 565 configured to provide a gas or fluid to an inside diameter of the separation capillary holder 570 so that, e.g., a nebulizing gas may be introduced in an inside diameter of the conductive tube 575 through the gas port 565, surround the separation capillary holder 570 and flow between an inner diameter of the conductive tube 575 and an outer diameter of the separation capillary holder 570 up to the tip portion 540. The nebulizing gas may also exit through the tip 542, further discussed below with respect to FIG. 5B, so as to mix with the sample ejected from the separation capillary 510 and nebulize the ionized sample. In examples, the assembly 500 may also include coolant tube nipples 525, which may be referred to as third lumen, configured to circulate coolant around the separation capillary 510.

[0031] FIG. 5B illustrates a configuration of the tip portion 540 of the assembly 500, in accordance with various examples of the disclosure. The tip portion 540 includes the tip 542 and is covered by a tip cover 545 that encompasses the tip portion 540 as well as a portion of the coupling sleeve 580 and may also encompass a portion of the separation capillary holder 570. In operation, the tip cover 545 may be configured to allow a nebulizing gas provided via the gas port 565 and flowing in a space between the outside diameter of the separation capillary holder 570 and the inside diameter of the conductive tube or rigid fitting 575 to mix with the liquid sample flowing from the separation capillary 510 at a location corresponding to the tip 542. Accordingly, at the tip 542, the nebulizing gas may nebulize any ions formed at the tip 542 and, e.g., reduce or eliminate the presence of “wet ions.” In other examples, the assembly 500 may include another lumen 515, referred to herein as fourth lumen 515, that is configured to flow a substance therethrough from the double lumen 520 to the tip 542.

[0032] This disclosure described some examples of the present technology with reference to the accompanying drawings, in which only some of the possible examples were shown. Other aspects can, however, be embodied in many different forms and should not be construed as limited to the examples set forth herein. Rather, these examples were provided so that this disclosure was thorough and complete and fully conveyed the scope of the possible examples to those skilled in the art.

[0033] Although specific examples were described herein, the scope of the technology is not limited to those specific examples. One skilled in the art will recognize other examples or improvements that are within the scope of the present technology. Therefore, the specific structure, acts, or media are disclosed only as illustrative examples. Examples according to the technology may also combine elements or components of those that are disclosed in general but not expressly exemplified in combination, unless otherwise stated herein. The scope of the technology is defined by the following claims and any equivalents therein.

Claims

CLAIMS1. A capillary emitter comprising: a coupling sleeve; a separation capillary inside the coupling sleeve, the separation capillary extending along a longitudinal axis of the coupling sleeve; a tip at an end of the coupling sleeve, the tip comprising an orifice and having an internal base; a first hollow internal cavity defined on one side thereof by the internal base in the coupling sleeve, the first hollow internal cavity comprising the separation capillary; and a fluid pathway within the first hollow internal cavity, the fluid pathway surrounding the separation capillary; wherein, at the internal base of the tip, the separation capillary and the fluid pathway are fluidly connected within the first hollow internal cavity.

2. The capillary emitter of claim 1, wherein an inside diameter of the orifice of the tip is in a range of 20 pm to 75 pm.

3. The capillary emitter of claim 2, wherein the inside diameter of the orifice of the tip is equal to about 30 pm.

4. The capillary emitter of any one of claims 1-3, wherein an outside diameter of the tip is in a range of 40 pm to 100 pm.

5. The capillary emitter of claim 4, wherein the outside diameter of the tip is equal to about 60 pm.

6. The capillary emitter of any one of claims 2-5, wherein an internal diameter of the separation capillary is equal to the inside diameter of the orifice of the tip.

7. The capillary emitter of any one of claims 1-6, wherein a material of the tip comprises a non-conductive material.

8. The capillary emiter of any one of claims 1-7, wherein a material of the tip comprises a refractory oxide.

9. The capillary emiter of claim 8, wherein the refractory oxide comprises a ceramic.

10. The capillary emiter of claim 8 or claim 9, wherein the refractory oxide comprises at least one of zirconium oxide, titanium carbonitride, alumina, and titanium nitride.

11. The capillary emiter of any one of claims 1-10, wherein the internal base of the tip has a substantially flat profile.

12. The capillary emiter of any one of claims 1-11, wherein the internal base of the tip is substantially perpendicular to the longitudinal axis of the separation capillary.

13. The capillary emitter of any one of claims 1-12, wherein the separation capillary abuts the internal base of the tip inside the first hollow internal cavity.

14. The capillary emiter of any one of claims 1-13, wherein: the capillary emiter is configured to be joined to a separation capillary holder; and a second hollow internal cavity inside the capillary emiter encompasses a portion of the separation capillary holder, the second hollow internal cavity being larger than the first hollow internal cavity.

15. The capillary emiter of claim 14, wherein the second hollow internal cavity and the portion of the separation capillary holder form a watertight seal.

16. The capillary emiter of claim 14 or claim 15, wherein the second hollow internal cavity and the portion of the separation capillary holder are held together via an adhesive.

17. The capillary emitter of claim 14 or claim 15, wherein the second hollow internal cavity and the portion of the separation capillary holder are held together via a sleeve.

18. The capillary emitter of any one of claims 1-17, wherein an outside diameter of the separation capillary is in a range of 100 pm to 360 pm.

19. The capillary emitter of claim 18, wherein the outside diameter of the separation capillary is equal to about 150 pm.

20. The capillary emitter of any one of claims 14-19, wherein the internal base of the tip and the separation capillary define a clearance therebetween.

21. The capillary emitter of claim 20, wherein the clearance is in a range of about 1 pm to about 20 pm.

22. The capillary emitter of claim 21, wherein the clearance is equal to about 10 pm.

23. The capillary emitter of any one of claims 1-22, wherein the internal base of the tip and the opening of the tip form an inlet comer at an intersection thereof, the inlet comer having a rounded profile.

24. A capillary assembly comprising: a housing; the capillary emitter of claim 1, wherein a first portion of the separation capillary of the capillary emitter is inserted in a separation capillary holder, and a second portion of the separation capillary of the capillary emitter is inserted in a first lumen; a conducting fluid capillary inserted in a second lumen parallel to the first lumen; a conductive fitting around the separation capillary holder along a longitudinal direction thereof; anda compression fitting around the separation capillary holder, the compression fitting being adjacent to the conductive fitting along the longitudinal direction of the separation capillary holder.

25. The capillary assembly of claim 24, wherein the first lumen is a central lumen and the second lumen is radially around the first lumen.

26. The capillary assembly of claim 24 or claim 25, further comprising a third lumen configured to flow a coolant therethrough, the third lumen being parallel to the first lumen and the second lumen.

27. The capillary assembly of any one of claims 24-26, wherein: the separation capillary is coupled to a sample source outside of the housing; and the conducting fluid capillary is coupled to a conducting fluid source outside of the housing.

28. The capillary assembly of any one of claims 24-27, further comprising: a tip cover encompassing an exit end of the separation capillary; a rigid fitting encompassing the separation capillary holder; and a nozzle in fluid communication with the tip cover via a port formed in the conductive fitting and via a space formed between the separation capillary holder and the rigid fitting.

29. The capillary assembly of claim 28, wherein the nozzle is configured to introduce a nebulizing gas to the tip cover via the space.

30. The capillary assembly of claim 29, wherein the tip cover is configured to mix the nebulizing gas with a liquid sample emitted from the capillary emitter.

31. The capillary assembly of any one of claims 24-30, further comprising a fourth lumen configured to flow a substance therethrough, the fourth lumen being parallel to the first lumen, the second lumen and the third lumen.

Images