Abstract:
A liquid junction assembly for providing a flow connection between two tubular conduits. The assembly includes respective bodies configured to define elongated passages of respective first and second cross sections to receive and locate the respective tubular conduits, a plate with at least one hole therethrough of a third cross section smaller than the first and second cross sections, and a seat for the plate, defined in a face of one or both of the bodies. The bodies and the plate are assembled with the plate in the seat and the elongated passages and the hole aligned along a common axis.

Description:
CROSS-REFERENCES TO RELATED APPLICATIONS 
       [0001]    This application claims priority from Australian Patent Application No. 2016902196, filed Jun. 6, 2016 incorporated by reference in its entirety. 
       FIELD OF THE INVENTION 
       [0002]    This invention relates generally to the joining of tubular conduits and more particularly to the joining of conduits of the scale employed in analytic systems such as liquid chromatography and mass spectrometry. The invention is especially useful where the tubular conduits are capillaries of submillimeter inner diameter, especially those involving nanoscale analytic volumes. 
       BACKGROUND 
       [0003]    Problems commonly arise in liquid chromatography from the dead volumes that can be created by any of the myriad of connections from the injection port to the column and from the column to the detector. Dead volume, or the lack thereof, is extremely critical after the column until the sample reaches the detector. These problems are exacerbated with capillary and low micro and nano-liquid chromatography mass spectrometry where bad connections can lead to a total failure of the experiment. The typical low flow rates in these applications make them exceptionally sensitive to dead volumes. While there has been significant development of minimal dead volume and ultra high pressure liquid chromatography (UHPLC) fittings to optimise simple connections (e.g. the Thermo NanoViper, the IDEX MarvelX fittings, and the Optimze Technologies EXP2 fittings), there are currently no reliable minimal dead volume unions for joining two capillaries. 
         [0004]    Current such unions, or ‘liquid junctions’, currently comprise a tubular body with axially aligned cylindrical passages to receive the respective capillaries. The passages are separated at the center of the body by a web in which is drilled a very small hole at the axial center line, to join the passages and thereby the bores of the capillaries. In a typical such system, the passage may be of 0.9 mm diameter and the hole 50 μm. The current manufacturing method entails drilling the hole using a drill bit or a laser beam. These methods are limited due to the distance from the end of the passage in the fitting to the web to be drilled. Typical limitations with mechanical drilling using drill bits range from approximately 75 to 200 μm and greater, depending on the capabilities of the machine shop, equipment used and drill bit sizes. Typical limitations of laser drilling are in the 30-60 μm range due to the distance of the laser head from the web in which the through hole is laser drilled. Correctly positioning the hole within, e.g., 50 μm of the center line is challenging, as alignment of the laser is done by camera and eye and is thus operator dependent. The laser beam must not touch the sides of the access passage, thus reducing cutting power. It is also difficult to flow the necessary gas down the hole for laser cutting. All of these factors impact the position of the through hole, which is quite critical in such small inner diameters of tubing that are used with the liquid junction. 
         [0005]    Another method currently used is to drill a large hole to accommodate the OD of the tubing, or in some instances tubing with an additional outer sleeve to increase the OD to fit through the larger drilled through hole. The tubing coming in from both sides is then butted together. This again can cause dead volume, should both tubes not fit exactly flush together, or even cause blockage due to hole misalignment. This method also relies on the user positioning each tube exactly half way in the fitting, in the case of a coned port union, so there is enough tubing protruding past the ferrule for it to bite or have purchase onto the tubing. 
         [0006]    It is an object of the invention to achieve a liquid junction especially adaptable at the micro or nanoscale in which the necessary hole accuracy is more easily achieved than with the aforementioned prior arrangements. 
         [0007]    Reference to any prior art in the specification is not an acknowledgment or suggestion that this prior art forms part of the common general knowledge in any jurisdiction or that this prior art could reasonably be expected to be understood, regarded as relevant, and/or combined with other pieces of prior art by a skilled person in the art. 
       SUMMARY OF THE INVENTION 
       [0008]    The invention broadly entails the concept of providing the required hole at the actual liquid junction by means of a discrete holed plate or shim element in place of the conventional integral web. 
         [0009]    The invention accordingly provides, in one aspect, a liquid junction assembly for providing a flow connection between two tubular conduits, comprising: 
         [0010]    respective bodies configured to define respective elongated passages of respective first and second cross sections to receive and locate the respective tubular conduits; 
         [0011]    a plate with at least one hole therethrough of a third cross section smaller than said first and second cross sections; and 
         [0012]    a seat for the plate, defined in a face of one or both of said bodies; 
         [0013]    wherein the bodies and the plate are assembled with the plate in the seat and the elongated passages and the hole aligned along a common axis. 
         [0014]    In a second aspect, the invention provides a kit for a liquid junction assembly for providing a flow connection between two tubular conduits, comprising: 
         [0015]    respective bodies configured to define elongated passages of respective first and second cross sections to receive and locate the respective tubular conduits; 
         [0016]    a plate with at least one hole therethrough of a third cross section smaller than said first and second cross sections; and 
         [0017]    a seat for the plate, defined in a face of one or both of said bodies; 
         [0018]    wherein the bodies and the plate are adapted to be assembled with the plate in the seat and the elongated passages and the hole aligned along a common axis. 
         [0019]    In an embodiment, the respective bodies are discrete bodies but in other embodiments they may be portions of a single integral body. 
         [0020]    The bodies and the plate may be assembled or adapted to be assembled together by a screw, thread or other mechanical connection between the bodies that traps the plate in the seat between the bodies. In an alternative arrangement, the bodies and optionally also the plate are diffusion bonded, or welded, to form the assembly. In another alternative arrangement, such as could be the case if glass were the body material, or body and plate material, heat or heat and pressure could be applied to bond the pieces together. Yet another arrangement involves the use of an adhesive to bond the pieces together such as in the case of a polymer used in the body material, or body and plate material. 
         [0021]    The elongated passages are typically cylindrical. The first and second cross sections may be equal or different for joining conduits of the same or different sizes. 
         [0022]    The plate is preferably a disc. The disc may for example be 25-100 μm thick and may be in any of a variety of materials including a metallic material such as 300 or 400 series stainless steel or titanium, a ceramic, a glass such as borosilicate or quartz, or a polymer such as PEEK or filled PEEK. 
         [0023]    The plate may contain a single hole, or a series or matrix of holes. The series of holes might be used in conjunction with multi-lumen tubing and/or a combination of tubing and emitter tips. 
         [0024]    The assembly or the components of the kit are preferably configured so that when the conduits are correctly located in the elongated passages, they squarely abut the respective sides of the plate so as to minimize any dead space and to accurately align the inner diameters of the conduits with the hole or holes in the plate. To that end, the plate preferably exhibits smooth parallel faces about the hole or holes. 
         [0025]    Each hole is typically of uniform circular cross section. The hole or holes may be drilled by any suitable means including a laser or ultrasound drill or formed in a drawing process in the case of a material such as glass. 
         [0026]    For application to the joining of capillary or nanoscale columns, for example in liquid chromatography and detection such as mass spectrometry, the elongated passages are preferably of a diameter in the range of 0.5 mm-2 mm. The hole may be of a diameter in the range 10 μm-200 μm, for example in the range 30-100 μm. 
         [0027]    The liquid junction assembly may typically be incorporated in a coupling assembly by which the conduits may be securely joined within the liquid junction assembly. Such a coupling may include, for example, threaded components configured to be clamped onto the respective conduits, preferably by application of finger force without assistance from external tools. 
         [0028]    As used herein, except where the context requires otherwise, the term “comprise” and variations of the term, such as “comprising”, “comprises” and “comprised”, are not intended to exclude further additives, components, integers or steps. 
         [0029]    These and other features and advantages of the present invention will become apparent from the following detailed description of preferred embodiments which, taken in conjunction with the accompanying drawings, illustrate by way of example the principles of the invention. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0030]      FIG. 1  is an exploded perspective view of a liquid junction assembly according to an embodiment of the invention; 
           [0031]      FIG. 2  is a side elevational view corresponding to  FIG. 1  but viewed from the other side; 
           [0032]      FIG. 2A  is an enlarged cross-sectional view of the disc component; 
           [0033]      FIG. 3  is a perspective view similar to  FIG. 1  of the assembled components; 
           [0034]      FIG. 4  is a side elevational view similar to  FIG. 2  of the assembled components; 
           [0035]      FIG. 5  is a side elevational view similar to  FIG. 2  of a modified embodiment in which the respective body components are adapted for a different coupling system; 
           [0036]      FIG. 6  is a cross-sectional view of the liquid junction assembly of  FIG. 1-4 or 5  in situ in a first coupling assembly joining two capillary tubes such as a column to an emitter tip, a tube to an emitter tip, or a column to a tube; 
           [0037]      FIG. 7  is a cross-sectional view of the liquid junction assembly of  FIG. 1-4 or 5  in situ in a second coupling assembly joining two capillary tubes such as a column to an emitter tip, a tube to an emitter tip, or a column to a tube; 
           [0038]      FIG. 8  is a cross-sectional view of the liquid junction assembly of  FIG. 1-4 or 5  in situ in a third coupling assembly joining two capillary tubes such as a column to an emitter tip, a tube to an emitter tip, or a column to a tube; and 
           [0039]      FIG. 9  is an exploded perspective view similar to  FIG. 1  of a further embodiment of the invention for use with multi-lumen tubing. 
       
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
       [0040]    Embodiments of a liquid junction assembly according to the invention are illustrated in  FIGS. 1-5 and 9 , and their incorporation in coupling assemblies for capillary columns in liquid chromatography and mass spectrometry is depicted in  FIGS. 6-8 . 
         [0041]    The liquid junction assembly  10  of  FIGS. 1-4  includes a pair of generally cylindrical bodies  20 ,  30  that are of similar configuration and coupled together by engagement of a reduced diameter spigot portion  22  on body  20  with a matching circular recess  32  on body  30 . Each body  20 ,  30  has a main portion  24 ,  34  of greatest diameter extending from an outer end face  25 ,  35 , joined by an optionally tapered portion  26 ,  36  to a reduced diameter inner portion  27 ,  37 . In the case of body  20 , spigot  22  of further reduced diameter extends from portion  27  to an end face  43  that forms the innermost end of the body, while for body  30  the reduced diameter portion  37  extends to an inner end face  37   a  of the body, in which recess  32  is formed. 
         [0042]    Extending coaxially through the respective bodies  20 ,  30  are bores  40 ,  50  that form elongated passages  41 ,  51  of respective but in this case equal diameters within reduced diameter portions  27 ,  37  and respectively open into the end face  43  of spigot  22  and into recess  32 . In other embodiments, the diameters of passages  41 ,  51  may not be equal so as to accommodate tubes or columns of different OD. At their outer ends, the bores  40 ,  50  are counterbored to provide enlarged threaded sockets  45 ,  55  for securing the respective bodies to components of a column coupling assembly  100  in the manner depicted in  FIG. 8 . In this case, the coupling assembly is a pair of SGE SilTite™ ferrule and nut couplings. The middle portion  26  of bore  40 ,  50  is tapered to accommodate the biconical ferrule  105  of this coupling, as illustrated in  FIG. 8 . 
         [0043]    Instead of being female threaded sockets, elements  45 ,  55  could be male threads for use with female nuts. 
         [0044]    The outer ends of main body portions  24 ,  34  of the bodies includes opposite flats  29 ,  39  for tool engagement. 
         [0045]    Located or trapped in recess  32  between the end face  43  of spigot  22  and the annular inner face  33  of the seat  32  is a plate, shim or wafer  60  in the form of a circular, in this case metallic, disc. The disc may typically be about 70 μm thick and has been laser drilled with a small central hole  61  sized to match the inner diameter of the capillary columns to be joined by the assembly, or to allow for optimized separation and detection performance. Typical diameters of the hole  61  are 25 or 50 μm for current commercial capillary or nano columns. In this case, disc  60  may typically be of a diameter in the range 1.2 to 2.0 mm. 
         [0046]    In this embodiment, the three components, the bodies  20 ,  30  and the disc  60 , are diffusion welded to form a unitary unit at the interfaces of reduced diameter portions  27 ,  37  and between the end face  43  of the spigot  22 , the disc  60  and the annular inner face  33  of recess  32 . In use, the assembly is incorporated as previously described within a coupling assembly  100  such as a SilTite™ coupling ( FIG. 8 ) with respective columns  102 ,  103  inserted into passages  41 ,  51  to firmly and squarely abut the disc  60  about the hole  61 . To facilitate the seal, the faces of disc  60  are smooth, polished or lapped. One option is to cleave disc  60 , if it were made out of glass and depending on its length. The coupling is secured by rotating the nuts  110  ( FIG. 8 ) to clamp the respective biconical ferrule  105  onto the capillary. 
         [0047]    An example of a SilTite™ coupling is disclosed in U.S. Pat. No. 8,128,131, the entire disclosure of which is incorporated herein by reference. 
         [0048]      FIG. 5  depicts an embodiment  10 ′ similar to that of  FIGS. 1-4  except that the tapered portion of the bore  40 ,  50  is not included. This embodiment is suitable for use with a coupling system such as the nanoViper assembly, as depicted in  FIG. 6 , or the Matrix assembly. 
         [0049]    In the embodiments illustrated in  FIGS. 1-5 , the components are diffusion bonded to form a permanent assembly. In an alternative arrangement  10 ″ ( FIG. 7 ), one body or the other may have a greater diameter and be extended at  90  the inner end to form an internally threaded opening  92  to receive a correspondingly threaded outer surface of the other body. A screwed assembly of this kind is depicted in  FIG. 7 , again as part of a SilTite™ coupling assembly  100 ″. 
         [0050]      FIG. 9  depicts a further embodiment  10  for use with multi-lumen tubing. In this embodiment, like parts are indicated by like reference numerals preceded by a “1”. In this case, shim/plate or disc  160  has a square array of four holes  161 . Correct alignment of the lumens of the tubing and the holes  161  is achieved by keyed engagements between the plate  160  and the bodies  120 ,  130 , and between the bodies and the tubes. The former of these keys is provided by engaging radial tabs  168 ,  128  on the plate  160  and on spigot  122 , with a matching radial channel (not visible) on recess  132  of reduced diameter inner portion  137 . The other key is between a longitudinal groove  148  of semi-circular cross-section along each passage  141 ,  151 , and a rib on the respective tube to rotationally align the tube lumens with holes  161 . 
         [0051]    It will be appreciated that the illustrated liquid junction assemblies have significant advantages over prior arrangements. Although multicomponent rather than integral, it may still be provided in a diffusion bonded permanent assembly but the manner in which the hole is provided between the capillary bores is more accurate and simpler. By readily providing good alignment on the axis of the system between the hole and the capillary columns, accidental dead volume is minimized or even potentially eliminated, a valuable advantage in analysis at micro and nano-scales. As depicted in  FIGS. 6-8 , the liquid junction assembly is readily compatible with a variety of coupling systems. 
         [0052]    Another advantage of this approach to providing a liquid junction is that a variety of combinations of hole diameters, end fittings and ports could be selected from a kit of selectable parts. 
         [0053]    There is complete flexibility in the materials employed to suit different applications. In the principal embodiment described above, the three components are metal so as to permit diffusion bonding. A suitable metal for the disc is 300 or 400 series stainless steel, but titanium would also be suitable. The disc could alternatively be formed in a ceramic, a glass such as borosilicate or quartz, or a polymer such as PEEK or filled PEEK. The components could be all glass. The respective bodies  20 ,  30  may be made in a conductive material in support of electrospray. For other applications, the bodies  20 ,  30  and/or the disc  60  might be made of titanium, or of a polymeric material or materials that may or may not be filled with other materials such as conductive fillers to allow for any inert yet conductive connection. Conductivity might be optimized by plating or doping of the disc and/or the bodies or any combination thereof. The assembly could be compatible with ultra-high pressure liquid chromatography and is readily manufacturable as an ultra-low dead volume union in the low nano liter range. 
         [0054]    It will be understood that the invention disclosed and defined in this specification extends to all alternative combinations of two or more of the individual features mentioned or evident from the text or drawings. All of these different combinations constitute various alternative aspects of the invention.