Abstract:
An NMR flow cell assembly comprises: a flow cell for holding a sample; inlet and outlet sample tubing providing fluidic access to the flow cell; and a pair of connectors connecting the inlet and outlet sample tubing to the flow cell. Each connector is secured to the flow cell by an adhesive region. The adhesive region is separated from the interior of the flow cell by an annular adhesive-separation barrier extending between the flow cell and said each of the pair of connectors. The barrier may be formed by an O-ring, or ridges formed in the flow cell wall. In another embodiment, the flow cell and connector have matching helical threads, and a sealing barrier such an O-ring or ferrule is placed along a transverse end face of the flow cell, such that the sealing force on the flow cell is longitudinal and/or outward.

Description:
FIELD OF THE INVENTION 
     The invention in general relates to nuclear magnetic resonance (NMR) spectroscopy, and in particular to NMR flow cell assemblies and methods. 
     BACKGROUND OF THE INVENTION 
     Nuclear magnetic resonance (NMR) spectrometers typically include a superconducting magnet for generating a static magnetic field B 0 , and an NMR probe positioned within a bore of the magnet. The NMR probe includes one or more special-purpose radio-frequency (RF) coils for applying a time-varying magnetic field B 1 , perpendicular to the field B 0  to samples of interest, and for detecting the response of the samples to the applied magnetic fields. The samples of interest are normally held in sample tubes or in flow cells. A sample tube or flow cell is positioned within an access bore of the NMR probe, and the probe is inserted into the magnet such that the sample is situated at or near the center of the static magnetic field. The sample temperature can be controlled by flowing air of a given temperature through the NMR probe access bore, along the sample tube or flow cell. 
     The design of NMR probes and associated flow cells is typically subject to tight spatial constraints. High-resolution NMR magnets have access bores with an inner diameter on the order of a few cm, for example 45 mm, and lengths on the order of 1 meter. Within the NMR probe, the internal access bore typically has an inner diameter of about 1 cm or less, and a length comparable to that of the magnet access bore. In an exemplary commercial implementation, the NMR probe access bore is 0.75 m long and less than 1 cm in diameter. It is generally desirable to minimize the distance between the flow cell and the RF coils because the quality of NMR measurements is directly related to the coil filling factor, or the fraction of coil volume occupied by sample. At the same time, if air flow is used to control the sample temperature, enough space must be left to accommodate the passage of air between the flow cell and the inner probe wall. 
     In the tight space normally available within the NMR probe, connecting a flow cell to sample inlet and outlet tubing can pose substantial design challenges. One approach to connecting the flow cell to the sample tubing is described by Haner et al. in U.S. Pat. No. 6,177,798. A flow-through NMR probe includes a replaceable NMR flow cell connected to sample tubing using compression-style fittings. The connections described by Haner et al. are inert, and do not interact chemically with the sample. At the same time, the flow tube assembly can have a diameter substantially larger than the diameter of the flow cell itself. 
     In the article “Adaptation of Commercial 500 MHz Probes for LCNMR,”  Journal of Magnetic Resonance  A 119:115–119 (1996), Barjat et al. describe a flow cell assembly in which the flow cell is epoxied to the inlet and outlet tubing. The outer diameter of the resulting assembly, shown in  FIG. 2  of Barjat et al., may be defined approximately by the flow cell diameter. At the same time, Barjat et al. report that, at least for some of their cells, compatibility between materials and solvents remains a significant problem, and the epoxy adhesive used is not ideal. 
     In U.S. Pat. No. 5,258,712, Hoffmann et al. describe a sample head for flowthrough NMR spectroscopy. The parts constituting an NMR vessel, namely a replaceable quartz cuvette, a cylindrical glass casing, a cover, and a base, can be clamped together with a single clamping device, as shown in  FIG. 2-A  of Hoffmann et al. To replace the a quartz cuvette in the system of Hoffmann et al., an end user would need access to the clamping device, and to the space between the cover and base, so as to remove the old cuvette and place the new cuvette between the cover and base. 
     SUMMARY OF THE INVENTION 
     According to one aspect, the present invention provides a nuclear magnetic resonance flow cell assembly for holding a nuclear magnetic resonance sample, comprising: a flow cell for holding the nuclear magnetic resonance sample; inlet and outlet sample flow tubing for providing fluidic access to the flow cell; and a pair of connectors including a first connector for connecting the inlet sample flow tubing to the flow cell, and a second connector for connecting the outlet sample flow tubing to the flow cell. Each of the pair of connectors is secured to the flow cell by an adhesive region, wherein the adhesive region is separated from the interior of the flow cell by an annular adhesive-separation barrier extending between the flow cell and said each of the pair of connectors. 
     According to another aspect, the present invention provides a nuclear magnetic resonance flow cell assembly for holding a nuclear magnetic resonance sample, comprising: a flow cell for holding the nuclear magnetic resonance sample; sample flow tubing for providing fluidic access to the flow cell; a connector for fluidically connecting the sample flow tubing to the flow cell; and a sealing barrier positioned between a transverse end surface of the flow cell and a transverse surface of the connector. The connector includes a flow cell connector bore sized to accommodate an end region of the flow cell. The flow cell has a first helical thread along a lateral surface of the flow cell. The connector has a second helical thread matching the first helical thread, for screwing the connector to the flow cell. The sealing barrier is pressed between the flow cell and the connector when the flow cell and the connector are screwed together, for sealing an interface between the flow cell and the connector. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The foregoing aspects and advantages of the present invention will become better understood upon reading the following detailed description and upon reference to the drawings where: 
         FIG. 1  is a schematic diagram of an exemplary NMR spectrometer according to an embodiment of the present invention. 
         FIG. 2-A  shows an isometric view of a flow cell assembly of the spectrometer of  FIG. 1-A , according to an embodiment of the present invention. 
         FIG. 2-B  shows a longitudinal sectional view of a part of the flow cell assembly of  FIG. 1-A  including a connection between a flow cell and sample tubing, according to an embodiment of the present invention. 
       FIGS.  3 -A–C show longitudinal sectional views of exemplary flow cell connection configurations suitable for use with enclosed adhesives, according to embodiments of the present invention. 
       FIGS.  4 -A–C show longitudinal sectional views of exemplary flow cell connection configurations suitable for establishing transverse-face, axial seals, according to embodiments of the present invention. 
       FIGS.  5 -A–C show isometric, transverse sectional and longitudinal sectional views of a connector according to an embodiment of the present invention. 
         FIG. 5-D  shows a longitudinal sectional view of a two-piece connector including the connector of FIGS.  5 -A–C and an extension piece, according to an embodiment of the present invention. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     In the following description, a set of elements includes one or more elements. Any reference to an element is understood to encompass one or more elements. The statement that a coil is used to perform a nuclear magnetic measurement on a sample is understood to mean that the coil is used as transmitter, receiver, or both. A transverse surface need not be perpendicular to the longitudinal axis defined by a flow cell assembly, and may include a tapered surface having a transverse component. 
     The following description illustrates embodiments of the invention by way of example and not necessarily by way of limitation. 
     Some NMR probes impose particularly demanding constraints on the design of the associated flow cell assemblies. For example, an exemplary cryogenically-cooled probe design uses a probe bore having half the diameter of a standard room-temperature probe bore. Moreover, a low-temperature probe may not be amenable to convenient removal from the magnet in order to facilitate replacement of the flow cell. For such a probe, the flow cell assembly is preferably replaced while the probe is held within the magnet. Typically, room-temperature probes may be removed from the magnet by an end user, in order to facilitate replacement of the flow cell assembly while the probe is situated on a workbench. 
     Conventional compression-style fittings as described by Haner et al. in the above-referenced U.S. Pat. No. 6,177,798 may not fit in the inner bores of some NMR probes. It was observed that simply scaling down the size of the compression-style fittings may not make the connectors suitable for use in narrow probe bores. Scaling down the fitting size can weaken the seals established by the fittings, allowing the sample to leak out of the connection. Weakening the seals can be particularly undesirable in applications requiring relatively high sample pressures. 
     Previously described adhesive-based connection approaches were also observed to be subject to undesirable problems. Swelling of the epoxy due to contact with the sample may make a conventional adhesive-based assembly design, such as the one described by Barjat et al., unacceptably short-lived for commercial applications. Furthermore, contact between epoxy and sample can lead to chemical contamination of analytical samples and flush solvents. 
     The preferred flow cell assembly configurations described below allow establishing radially-compact, high-longevity, high-sealing-force connections between NMR flow cells and associated sample tubing, without exposing the analytical samples and flush solvents to unacceptably high contamination risks. The flow cell assemblies may be replaced by an end user through the NMR probe central bore while the probe is kept in the NMR spectrometer magnet. The preferred flow cell assemblies are particularly suited for applications subject to tight spatial constraints and/or access limitations, and for high-pressure applications. 
       FIG. 1  is a schematic diagram illustrating an exemplary nuclear magnetic resonance (NMR) spectrometer  12  according to an embodiment of the present invention. Spectrometer  12  comprises a magnet  16 , an NMR probe  20  inserted in a cylindrical bore of magnet  16 , and a control/acquisition system  18  electrically connected to magnet  16  and probe  20 . Magnet  16  includes an access/guide tube  27   a , which allows access to NMR probe  20  from the top of magnet  16 . Probe  20  includes one or more radio-frequency (RF) coils  24 . A flow cell assembly  22  is positioned within probe  20 , for holding an NMR sample of interest within coil(s)  24  while measurements are performed on the sample. Flow cell assembly  22  includes a flow cell  26 , sample inlet tubing  30   b  fluidically connected to an inlet end of flow cell  26 , and sample outlet tubing  30   a  fluidically connected to an outlet end of flow cell  26 . Sample inlet tubing  30   b  may be connected to a liquid chromatography (LC) apparatus or another known sample source. In the illustrated configuration, sample outlet tubing  30   a  extends out of probe  20  on the side opposite sample inlet tubing  30   b , through access tube  27   a . The sample outlet tubing may also extend back down through probe  20 . 
     An upper support disk  25   a  and a lower support disk  25   b  may be used to support flow cell assembly  22 , coil(s)  24  and associated components within probe  20 . Two guide tubes  27   a–b  may be provided on opposite sides of disks  25   a–b , to facilitate the insertion and removal of probe assembly  22  into and from probe  20 . Flow cell assembly  22  may be inserted into and removed from probe  20  from above, through the central apertures defined in support disks  25   a–b . An end user may replace flow cell assembly  22  through the central NMR probe bore, while the NMR probe is situated in the NMR magnet. In a present implementation, an end user inserts and removes flow cell assembly  22  from above. In alternative implementations, an end user may insert and/or remove a flow cell assembly from above and/or below. 
     To perform a measurement, a sample is inserted through inlet tubing  30   b  into flow cell  26 . Magnet  16  applies a static magnetic field B 0 , to the sample held within flow cell  26 . Control/acquisition system  18  comprises electronic components configured to apply desired radio-frequency pulses to probe  20 , and to acquire data indicative of the nuclear magnetic resonance properties of the samples within probe  20 . Coils  24  are used to apply radio-frequency magnetic fields B 1 , to the sample, and/or to measure the response of the sample to the applied magnetic fields. The RF magnetic fields are perpendicular to the static magnetic field. The same coil may be used for both applying an RF magnetic field and for measuring the sample response to the applied magnetic field. Alternatively, one coil may be used for applying an RF magnetic field, and another coil for measuring the response of the sample to the applied magnetic field. Once the desired NMR data has been collected, the sample is removed from flow cell  26  either through inlet tubing  30   b  or through outlet tubing  30   a . A flushing solvent is run through tubing  30   a–b  and flow cell  26 , to clean flow cell assembly  22  before another NMR sample is inserted. 
       FIG. 2-A  shows an isometric view of flow cell assembly  22 , while  FIG. 2-B  shows a longitudinal sectional view of an interconnect region of flow cell assembly  22 , at the interface between flow cell  26  and outlet tubing  30   a , according to an embodiment of the present invention. A connection configuration similar to that shown in  FIG. 2-B  may be used at the interface between flow cell  26  and inlet tubing  30   b . Flow cell  26  is connected to inlet and outlet sample tubing  30   a–b  through corresponding connectors  32   a–b . Each connector  32   a–b  may have longitudinal channels defined on its outer surface, to allow temperature control gas (e.g. air or nitrogen) to flow longitudinally along flow cell  26 . One or both of connectors  32   a–b  may be used to attach flow cell assembly  22  to the support structure of probe  20 . For example, connector  32   a–b  may rest on a matching tapered (e.g. frusto-conical) surface defined by upper support disk  25   a , shown in  FIG. 1 . 
     As shown in  FIG. 2-B , flow cell  26  defines a sample-holding chamber  33  for holding the sample of interest, and an access channel  34  extending between sample-holding chamber  33  and an external opening  36 . Access channel  34  has a smaller inner diameter than sample-holding chamber  33 . The thicker wall of flow cell  26  at its ends provides increased mechanical stability to flow cell  26 . Outlet connector  32   a  fluidically connects outlet tubing  30   a  to flow cell  26 . Connector  32   a  has a lateral wall enclosing a cylindrical flow-cell connector bore  40 , a cylindrical sample tubing connector bore  44 , and an annular block  46  separating the two opposite bores  40 ,  42 . Flow cell connector bore  40  is sized to accommodate an end region of flow cell  26 , while sample tubing connector bore  44  is sized to accommodate an end region of outlet tubing  30   a . Annular block  46  has a central longitudinal aperture  48  extending therethrough, for allowing the passage of sample fluid. 
     Flow cell  26  is secured to connector  32   a  by an enclosed adhesive  50  situated between the outer surface of flow cell  26  and the inner surface of connector bore  40 . Adhesive  50  is bounded at opposite longitudinal ends by two annular, transverse barriers extending from the outer surface of flow cell  26  to the inner surface of connector bore  40 . The annular barriers are preferably formed by O-rings  52   a–b . O-rings  52   a–b  are partially enclosed within corresponding annular counterbores (grooves)  53   a–b  formed in connector  32   a  along the inner surface of connector bore  40 . The depth of counterbores  53   a–b  (the enclosed radial extent of O-rings  52   a–b ) is preferably between ¼ and ¾ of the cross-section of O-rings  52   a–b . An internal O-ring  52   a  isolates adhesive  50  from the sample liquid flowing through flow cell  26 . An external O-ring  52   b  provides an additional barrier between the sample liquid and the exterior of flow cell  26 , and centers flow cell  26  within connector bore  40  during the process of attaching flow cell  26  to connector  32   a . Additional adhesive  51  situated outside O-ring  52   b  further secures flow cell  26  to connector  32   a.    
     Similarly, tubing  30   a  is secured to connector  32   a  by an enclosed adhesive  60  situated between the outer surface of tubing  30  and the inner surface of connector bore  42 . Adhesive  60  is enclosed at opposite longitudinal ends by O-rings  62   a–b . O-rings  62   a–b  are partially enclosed within corresponding annular counterbores  63   a–b  formed in connector  32   a  along the inner surface of connector bore  44 . Additional adhesive  61  is provided outside O-ring  62   b . The configuration described above may be used for one or both of inlet and outlet connectors  32   a–b.    
     Flow cell  26  is preferably made of an NMR-compatible material such as quartz, borosilicate glass (Pyrex®), sapphire, ceramic, or high-performance plastic. Tubing  30   a–b  is preferably made of a flexible LC-compatible material such as polyetheretherketone (PEEK), polytetrafluoroethylene (PTFE, or Teflon®) or fused silica. Tubing  30   a–b  may also be made of a rigid material such as stainless steel. Connectors  32   a–b  may be made of polyetheretherketone, polytetrafluoroethylene, chlorotrifluoroethylene (CTFE, or Kel-F®), or other LC-compatible materials. The adhesive used to secure flow cell  26  and tubing  30   a–b  to connector  32  may be a two part adhesive such as an epoxy adhesive, e.g. EPON® high-performance epoxy. O-rings  52   a–b ,  62   a–b , may be made of inert, non-absorbent materials such as fluorocarbons/perfluoroelastomers, e.g. Simriz®. 
     The dimensions of flow cell  26 , tubing  30   a–b , and connector  32  may be chosen according to the particular NMR application envisioned. In an exemplary configuration, flow cell  26  may have an outer diameter of about 2–5 mm, an inner diameter at its ends of about 0.5–1 mm, and a length of 10–20 cm. Tubing  30  may have an outer diameter of about 1–3 mm, and an inner diameter of 0.1–0.5 mm. Connector  32  may have an outer wall thickness of 0.25–2.5 mm, and a longitudinal extent of 2.5–75 mm. The longitudinal extent covered by adhesive may be 5 to 40 mm. O-rings  52   a–b ,  62   a–b  may have a transverse cross-section on the order about 1 to 2 mm and an inside diameter on the order of about 0.5 to 3 mm. 
     Flow cell assembly  22  may be assembled outside probe  20 , by inserting O-rings  52   a–b ,  62   a–b  into corresponding connector bores  50 ,  44  and positioning the O-rings  52   a–b ,  62   a–b  into the corresponding annular counterbores  53   a–b ,  63   a–b . Adhesive is disposed evenly along the internal lateral surface between the internal O-rings  52   a ,  62   a  and their corresponding external O-rings  52   b ,  62   b . Flow cell  26  and tubing  30   a–b  are inserted into the corresponding bores of connectors  32   a–b  through the inner diameters of the O-rings  52   a–b ,  62   a–b . During assembly, internal O-rings  52   a ,  62   a  restrict uncured adhesive from transferring into the bottom-regions of the connector bores  40 ,  44  and once the adhesive has cured, O-rings  52   a ,  62   a  isolate the adhesive from sample fluids inserted into flow cell  26 . After the adhesive has cured, flow cell assembly  22  may be inserted into probe  20  through guide tube  27 , and secured to upper support disk  25   a  and/or lower support disk  25   b  (shown in  FIG. 1 ). A sample of interest is then inserted into flow cell  26  through inlet tubing  30   a , and removed from flow cell  26  either through inlet tubing  30   b  or through outlet tubing  30   a . Flushing solvent may also be run through flow cell  26 , to clean flow cell  26 . 
       FIG. 3-A  shows a longitudinal sectional view of part of a flow cell assembly  122  including the interface between a flow cell  126  and a connector  132 , according to another embodiment of the present invention. Connector  132  includes two sets of radial ridges  152   a–b  sized to accommodate flow cell  126  in a sliding fit. Ridges  152   a–b  are preferably integrally formed with connector  132 , i.e. are part of a single monolithic structure. Alternatively, ridges  152   a–b  may be provided as part of one or two sleeves secured to connector  132 . An adhesive  150  binds flow cell  126  to connector  132  along a surface bounded longitudinally by ridges  152   a–b . Ridges  152   a–b  act as barriers preventing the contact of adhesive  150  with fluids such as samples or flushing solvents. Using two set of ridges also provides for centering flow cell  126  within connector  132 . In an exemplary implementation, each set of ridges  152   a–b  may have a transverse size of 0.25 to 1.25 mm, and extend over a length of 2.5–12.5 mm. A ridged contact surface as described above may also be used to provide isolation for the adhesive used to secure the sample inlet and/or outlet tubing. Adhesive-isolation ridges positioned as described above may also be provided on the outer surface of a flow cell and/or sample tubing, instead of or in addition to ridges provided on the inner surface of a connector. Adhesive-isolation barriers comprising ridges may be more difficult to manufacture than O-rings, but may simplify the flow cell assembly by eliminating the need to place O-rings during the assembly process. Furthermore, using ridges reduces the potential for sample contamination that may be introduced by the use of O-rings. 
       FIG. 3-B  shows a longitudinal sectional view of part of a connector  232  according to another embodiment of the present invention. Connector  232  includes a generally-radial adhesive-insertion channel  255  extending from the external surface of connector  232  to the internal surface of one of the bores of connectors  232 . Connector  232  may include multiple such channels disposed at different azimuthal locations along connector  232 . Such channels may be used to inject adhesive in the connection space defined between connector  232 , the outer surface of a flow cell or sample tubing, and radial barriers formed by O-rings or ridges as described above. In an exemplary implementation, channel  255  may have a diameter of about 0.25–1.25 mm 
       FIG. 3-C  shows a connector  332  having an annular counterbore (groove)  355  serving as an adhesive reservoir. Counterbore  355  has a semi-circular longitudinal cross-section. Counterbore  355  is positioned along the connection space defined between connector  332 , the outer surface of a flow cell or sample tubing, and radial barriers formed by O-rings or ridges as described above. Counterbore  355  may be connected to an adhesive insertion channel such as the one shown in  FIG. 3-B . In an exemplary implementation, counterbore  355  may have a depth of about 0.1–1 mm, for example about 0.5 mm. A suitable counterbore may be helical rather than planar. A helical counterbore may be conveniently formed in connector  332  by twisting a tapping tool within the corresponding connector bore of connector  332 . An annular or helical adhesive-holding counterbore reduces the risk that adhesive is completely squeezed out of some azimuthal section of the contact surface defined between connector  332  and its corresponding flow cell or sample tubing. Such a counterbore thus facilitates establishing a uniform, secure connection between connector  332  and the flow cell or sample tubing. An annular or helical sample-holding reservoir as described above may also be defined along the outer surface of a flow cell or sample tubing, rather than along the inner surface of connector  332 . 
       FIG. 4-A  shows a longitudinal sectional view of part of a flow cell assembly  422  including the interface between a flow cell  426  and a connector  432 , according to another embodiment of the present invention. Connector  432  and flow cell  426  have matching helical threads  450   a–b  defined along a lateral internal bore surface of connector  432  and a lateral external surface of flow cell  426 , respectively. Connector  432  has a section of its lateral internal bore surface without threads that serves as an O-ring groove  462 . Connector  432  laterally encloses flow cell  426  along a longitudinal end section of flow cell  426 . An O-ring  452  is disposed between flow cell  426  and connector  432  along a transverse end face of flow cell  426 . O-ring  452  is pressed between flow cell  426  and connector  432  as the two parts are screwed together.  FIG. 4-A  depicts the O-ring under compression as its cross-section is distorted somewhat from the uncompressed circular cross-section typical of commercial O-rings. In the present embodiment, the dimension of the outer diameter of the uncompressed O-ring  452  is selected to fit closely with the inner wall of the O-ring groove  462  of connector  432  so that the transverse position of the O-ring  452  does not shift significantly during assembly and compression. In the present embodiment, the dimension of the inner diameter of the uncompressed O-ring  452  is selected so that its inner diameter under compression is approximately equal to the inner diameter of the flow cell  426 . The selection of the inner and outer diameters of O-ring  452  reduces the possibility of restriction or blockage of fluid flow due to any overlap with the inner diameter of the flow cell  426 . Also, this selection of the inner diameter of the O-ring  452  minimizes the volume of the axial gap  472  between the connector  432  and flow cell  426 . The optimal design of the inner and outer diameters of O-ring  452  provides maximum contact area along the transverse end surfaces of connector  432  and flow cell  426  for a stronger seal. O-ring  452  is preferably sufficiently slippery such that it is not subject to excessive torsional forces as flow cell  426  and connector  432  are screwed together. The sealing force on O-ring  452  and flow cell  426  is longitudinal. O-ring  452  establishes a leak-resistant seal between flow cell  426  and connector  432 . Placing the sealing interface along a transverse surface, rather than a lateral surface, allows a reduction in the lateral pressure needed to establish the seal. 
       FIG. 4-B  shows a longitudinal sectional view of part of a flow cell assembly  522  including the interface between a flow cell  526  and a connector  532 , according to another embodiment of the present invention. Flow cell assembly  522  differs from the assembly  452  shown in  FIG. 4-A  in that a ferrule  552  is used instead of an O-ring  452  to establish a leak-resistant seal between the flow cell and connector. The sealing force on ferrule  552  and flow cell  526  has a longitudinal component, and a transverse outward-directed component. Exemplary suitable materials for ferrule  552  include Tefzel®, PEEK, Kel-F®, and PTFE. In an exemplary embodiment, ferrule  552  may have an inner diameter of about 2.5–5 mm, e.g. 3.2 mm, and an outer diameter of 2.5 to 12.5 mm, e.g. 4 mm. Relative to O-rings, ferrules may pose a lesser risk of absorbing and releasing contaminants. 
       FIG. 4-C  shows a longitudinal sectional view of part of a flow cell assembly  622  including the interface between a flow cell  626  and a connector  632 , according to another embodiment of the present invention. Sample tubing  630  may be secured within connector  632  by known methods. Connector  632  and flow cell  626  have matching helical threads  650   a–b  defined along a lateral external surface of connector  632  and a lateral internal bore of flow cell  626 , respectively. Flow cell  626  laterally encloses connector  632  along a longitudinal end section of flow cell  626 . A ferrule  652  laterally encloses sample tubing  630 , and has a tapered external distal surface matching a corresponding tapered, transverse internal bore surface  654  of flow cell  626 . Ferrule  652  is pressed onto sample tubing  630  as connector  632  and flow cell  626  are screwed together. As the two parts are screwed together, ferrule  652  is pressed between the lower transverse surface of connector  632  and the tapered surface  654  of flow cell  626 . Alternatively, an inward-facing transverse tapered surface may be provided along the bottom of connector  632 , with the orientation of the tapered surface and the ferrule upside-down with respect to the orientation shown in  FIG. 4-C . 
     According to another embodiment of the present invention, the threaded connection configuration of  FIG. 4-A  is employed at the interface between a connector and a flow cell, while the enclosed-adhesive configuration of  FIG. 2-B  is employed at the interface between the connector and corresponding sample tubing. For sample tubing having a relatively small diameter, it may be difficult to define a thread in the sample tubing wall. Such a thread may be easier to form in the outer wall of a flow cell, which typically has a larger diameter than corresponding sample tubing. 
       FIG. 5-A  shows an isometric view of a connector  832  according to another embodiment of the present invention. FIGS.  5 -B–C show transverse and longitudinal sectional views of connector  832 . Connector  832  includes a main body  860  and a tubular lateral cover  862  having a smaller transverse size than body  860 . A transverse end surface  864  of body  860  may rest on a tapered transverse surface of a support disk. A plurality of longitudinal temperature-control gas channels  880  are defined along the outer surface of body  860 , for allowing temperature-control gas to pass along connector  832 . As shown in  FIG. 5-C , a flow cell connector bore  840  facing one end of connector  832   b  is sized to accommodate a corresponding flow cell, while a sample tubing connector bore  842  facing the other connector end is sized to accommodate corresponding sample tubing. A helical connection thread  850  is defined in the proximal (inner) region of flow cell connector bore  840 , for mating with a corresponding flow cell helical thread. The sample tubing may be connected to connector  832  using a thread or enclosed adhesive, as described above. 
       FIG. 5-D  shows a longitudinal sectional view of a two-piece connector  932  incorporating connector  832  and a tubular extension part  933  secured to connector  832 . Extension part  933  laterally encloses tubular extension  862 , and may be secured to tubular extension  862  by adhesive. Extension part  933  has a terminal tapered outer surface  935  at its distal end. A plurality of temperature-control gas channels extend along extension part  933 , including along tapered surface  935 . Each temperature control gas channel along extension part  933  and a corresponding temperature control gas channel along connector  832  forms part of a longer channel extending over the entire longitudinal extent of connector  932 . Outer surface  935  may rest on matching tapered surface of a support disk. Extension part  933  permits centering a standard flow cell having a predetermined length in the sweet spot of a given NMR probe. A two-part design is preferred for connector  932  in order to facilitate the machining of thread  850  along the inner surface of connector  832 . Machining a helical thread inside a deep bore may be difficult in practice. Thread  850  may be machined before connector  832  and extension part  933  are secured together. A two-piece connector design as shown in  FIG. 5-D  may also be used in an isolated-adhesive flow cell assembly as shown in  FIG. 2-A , to facilitate the step of securing the connector to the flow cell and/or sample tubing. A thread may also be defined along the inner surface of extension  862 . 
     The preferred enclosed-adhesive and end-face sealing connection designs described above allow reliable operation of NMR flow cell assemblies for extended time periods, while allowing an end user to conveniently replace the flow cell assemblies under tight spatial constraints. A connection design similar to that illustrated in  FIG. 2-B , held motionless and without adhesive, was observed to operate without a leak for a period of three months at atmospheric pressure. The preferred designs described above also allow operation of NMR flow cell assemblies at high pressures, e.g. above 3 MPa, and insertion and removal of the flow cell assemblies into and out of an NMR probe maintained inside the NMR magnet. The preferred threaded designs also allow an end user to assemble and reassemble the described assemblies in the field. 
     The above embodiments may be altered in many ways without departing from the scope of the invention. For example, the isolated-adhesive and end-face seal connections described above may be used at the flow cell and/or sample tubing connector ends. Adhesive may be used in conjunction with a threaded connection. A single O-ring, or more than two O-rings or other barriers may be employed between a connector and a flow cell or sample tubing. The directions of sample flow described above may be reversed. For example, the inlet tubing may be provided from above the flow cell, and the corresponding outlet tubing may be provided below or above the flow cell. Temperature-control gas channels extending along a connector may run through a connector, and/or along the external surface of the connector. Accordingly, the scope of the invention should be determined by the following claims and their legal equivalents.