COUPLING DEVICE FOR AN NMR FLOW CELL

Abstract

A flow cell assembly for use in NMR measurements on a liquid NMR sample in an NMR spectrometer has a cylindrical flow cell for receiving the NMR sample, with a first opening at a first end and a second opening at a second end, and a connecting piece arranged at the first opening for connecting a flow line to the flow cell in a fluid-tight manner. An opening diameter d.sub.op of the first opening is smaller than an inner flow cell diameter d.sub.in, and a sealing head of the connecting piece is arranged in the first opening, with a sealing head diameter d.sub.seal larger than d.sub.op. For NMR measurements, the flow cell assembly is modified in such a way that the flow lines can be easily exchanged, and high-quality NMR flow measurements can be carried out independently of the orientation of the magnetic field in the NMR spectrometer.

Claims

1. A flow cell assembly for use in an NMR spectrometer for performing NMR measurements on a liquid NMR sample, the assembly comprising: a flow cell for receiving the NMR sample, the flow cell forming a first opening at a first end of the flow cell and a second opening at a second end of the flow cell, and being substantially hollow-cylindrical along a longitudinal axis (A.sub.L); and a connecting piece for connecting a flow line to the flow cell in a fluid-tight manner, the connecting piece being arranged at the first opening of the flow cell, wherein an opening diameter d.sub.op of the first opening of the flow cell is smaller than an inner flow cell diameter d.sub.in, and a sealing head of the connecting piece is arranged in the first opening of the flow cell, and a sealing head diameter d.sub.seal of the sealing head of the connecting piece is larger than the opening diameter d.sub.op of the first opening of the flow cell.

2. The flow cell assembly according to claim 1, wherein an outer contour of the sealing head is substantially the same as an inner contour of the flow cell in a region of the first opening.

3. The flow cell assembly according to claim 1, wherein the sealing head has at least one sealing element along the longitudinal axis (A.sub.L) of the flow cell (11), the at least one sealing element being arranged between an inner wall of the flow cell and an outer wall of the sealing head.

4. The flow cell assembly according to claim 3, wherein the at least one sealing element is configured as a profile seal or contour seal.

5. The flow cell assembly according to claim 3 wherein, in a region of the sealing element, the sealing head has at least one annular peripheral groove in which a sealing ring can be accommodated.

6. The flow cell assembly according to claim 3, wherein the at least one sealing element has an elastic or liquid sealing material.

7. The flow cell assembly according to claim 1, wherein a connection diameter d.sub.con of the sealing head of the connecting piece is larger than an outer diameter d.sub.out of a sealing neck of the connecting piece.

8. The flow cell assembly according to claim 7, wherein the outer diameter d.sub.out of the sealing neck (14b) of the connecting piece (14) is smaller than a flow cell outer diameter d.sub.fout of the flow cell (11).

9. The flow cell assembly according to claim 1 wherein, in a region outside the flow cell, the connecting piece has an opening having a receiving diameter d.sub.rec for receiving a flow line.

10. The flow cell assembly according to claim 9 wherein, in a region within the flow cell, the sealing head of the connecting piece has an opening having a transfer diameter d.sub.tran for transferring the liquid NMR sample.

11. The flow cell assembly according to claim 10, wherein to the receiving diameter d.sub.rec and the transfer diameter d.sub.tran, the following applies: d.sub.tran<d.sub.rec.

12. The flow cell assembly according to claim 1, wherein an inner line diameter did of a connecting line in the sealing head of the connecting piece is greater than an outer line diameter d.sub.old of the connecting line.

13. The flow cell assembly according to claim 1, wherein the flow cell assembly is designed for an internal pressure of at least 10 bar.

14. An NMR spectrometer for measuring NMR samples, comprising: a flow cell assembly according to claim 1; a magnet bore in an NMR magnet arrangement; and a sample holder within the magnet bore for reversible insertion of the flow cell assembly.

15. The NMR spectrometer according to claim 14, wherein the NMR magnetic field (B.sub.0) generated by the NMR magnet arrangement runs transversely to an axis (A.sub.m) of the magnet bore.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0056] The invention is illustrated in the drawings and will be explained in more detail with reference to embodiments. In the drawings:

[0057] FIG. 1 shows a detail of a schematic longitudinal section of a flow cell assembly according to the invention with a partially shown flow cell and a connecting piece;

[0058] FIG. 2 shows the schematic longitudinal section of the flow cell assembly according to the invention from FIG. 1 with and without hatching to illustrate the flow spaces for a liquid NMR sample; and

[0059] FIG. 3 is a schematic view of a measurement setup for carrying out an NMR measurement using an NMR spectrometer and the flow cell assembly according to the invention.

DETAILED DESCRIPTION

[0060] FIG. 1 shows a schematic longitudinal section of a portion of a flow cell assembly 10 according to the invention as can be used in an NMR spectrometer for NMR measurement of a liquid NMR sample. The flow cell assembly 10 extends along a longitudinal axis A.sub.L.

[0061] The flow cell assembly 10 includes a flow cell 11 (“sample tube”) in which the liquid NMR sample is received. The flow cell 11 is substantially cylindrical and has a flow cell outer diameter d.sub.fout of approximately 5 mm, an inner flow cell diameter d.sub.in of approximately 4 mm and a total length along the longitudinal axis A.sub.L of approximately 180 mm (in FIG. 1 only a lower portion of the flow cell 11 of approximately 10 mm length is shown). In the embodiment shown here, the flow cell 11 is made of borosilicate glass 3.3.

[0062] A first opening 12 having an opening diameter d.sub.op of approximately 3.5 mm (i.e., approximately 87% of the inner flow cell diameter d.sub.in) is formed at a first end 13 of the flow cell 11 and a second opening is formed at a second end of the flow cell 11 (not shown in detail). The inner flow cell diameter d.sub.in tapers to the opening diameter d.sub.op along the longitudinal axis A.sub.L over a height H.sub.c of approximately 0.7 mm (i.e., somewhat less than 0.5% of the total length of the flow cell 11).

[0063] With regard to the first opening 12 at the first end 13 and the second opening at the second end, the flow cell 11 is not symmetrical in the embodiment shown. This means that the first opening 12 and the second opening are not identical in shape. In the embodiment shown here, the second opening at the second end of the flow cell 11 is designed without tapering (not shown in more detail). In other embodiments not shown here, it is also possible for the second opening at the second end of the flow cell 11 to widen.

[0064] The flow cell assembly 10 further includes a connecting piece 14 arranged at the first opening 12 at the first end 13 of the flow cell 11. The connecting piece 14 is divided into a sealing head 14a (also referred to as a “spigot” or “coupling”) and a sealing neck 14b. A sealing head diameter d.sub.seal of the sealing head 14a is approximately 3.9 mm and is therefore minimally smaller than the inner flow cell diameter d.sub.in (=4 mm) of the flow cell 11. An outer diameter d.sub.out of the sealing neck 14b is approximately 2.75 mm and is therefore smaller than the opening diameter d.sub.op (=3.5 mm) of the flow cell 11. The sealing head 14a, which has the sealing head diameter d.sub.seal of 3.9 mm, tapers at the transition to the sealing neck 14b, over a height H.sub.c of the connecting piece 14 of approximately 0.6 mm, to a connection diameter d.sub.con of approximately 3.4 mm.

[0065] In the embodiment shown here, d.sub.in (=4 mm)≥d.sub.seal (=3.9 mm)>d.sub.op (=3.5 mm)>d.sub.con (=3.4 mm)>d.sub.out (=2.75 mm). This enables the connecting piece 14 to be inserted securely, and the flow cell 11 and the connecting piece 14 form a tight positive fit.

[0066] The connecting piece 14 is inserted into the flow cell 11 in order to produce the flow cell assembly 10. This is possible because the outer diameter d.sub.out of the sealing neck 14b of 2.75 mm is smaller, and the sealing head diameter d.sub.seal of the sealing head 14a of 3.9 mm is slightly smaller than the inner flow cell diameter d.sub.in of the flow cell 11 of 4 mm. The first opening 12 having the opening diameter d.sub.op of 3.5 mm is large enough that the sealing neck 14b having the outer diameter d.sub.out of 2.75 mm can be guided out of the flow cell 11 while the sealing head 14a remains inside the flow cell 11 and forms a positive fit with the flow cell 11. The connection diameter d.sub.con of the sealing head 14a of 3.4 mm is slightly smaller than the opening diameter d.sub.op (=3.5 mm) of the first opening 12 at the first end 13 of the flow cell 11. Therefore, the sealing head 14a cannot be pushed beyond the first opening 12 of the flow cell 11 since the sealing head diameter d.sub.seal is larger than the opening diameter d.sub.op of the first opening 12.

[0067] In the embodiment shown here, the connecting piece 14 has a length of approximately 10 mm along the longitudinal axis A.sub.L. The sealing head 14a occupies a region 26 within the flow cell 11, the length of the sealing head 14a along the longitudinal axis being approximately 4.5 mm. The sealing neck 14b occupies a region 24 external to the flow cell 11, the length of the sealing neck 14b along the longitudinal axis being approximately 5.5 mm.

[0068] In a region 18 of the first opening 12, there is both the tapering of the flow cell 11 and the tapering of the sealing head 14a. In the embodiment shown here, an outer contour 16 of the sealing head 14a is designed in such a way that it substantially corresponds to an inner contour 17 of the flow cell 11. In this way, a particularly stable positive fit is achieved and the seal between the flow cell 11 and the connecting piece 14 is improved.

[0069] The sealing head 14a comprises two sealing elements 19. In the embodiment shown here, the sealing elements 19 are designed in the form of two sealing rings 19a. The sealing rings 19a are arranged along the longitudinal axis A.sub.L between an inner wall 20 of the flow cell and an outer wall 21 of the sealing head 14a and embedded in an annular peripheral groove 23. As a result of the groove 23, the sealing rings 19a can be securely attached to the sealing head 14a. The groove 23 extends over a region 22 which comprises approximately the central region along the longitudinal axis A.sub.L in the sealing head 14a. In further embodiments not shown here, it is also possible for only one sealing element 19 or for three sealing elements 19 to be present. The sealing elements 19 improve the seal between the flow cell 11 and the connecting piece 14 and also ensure that the sealing head 14a is additionally clamped within the flow cell 11.

[0070] Furthermore, the sealing head 14a comprises a connecting line 28 having an outer line 28a and an inner line 28b. In the embodiment shown here, the connecting line 28 is substantially cylindrical and has a length of approximately 4 mm along the longitudinal axis A.sub.L. The outer line 28a has an outer line diameter d.sub.old of approximately 0.8 mm and a length along the longitudinal axis A.sub.L of approximately 1 mm. The inner line 28b has an inner line diameter did of approximately 2 mm and a length along the longitudinal axis A.sub.L of approximately 3 mm.

[0071] A liquid NMR sample is conducted, via the outer line 28a, from the first opening 12 further into the inner line 28b and from there into the flow cell 11. The liquid NMR sample flows through the flow cell 11 in a uniform flow due to the larger inner line diameter did of the connecting line 28. The rounded contour widening at the transition from the outer line 28a to the inner line 28b also ensures a uniform flow of the liquid NMR sample out of or into the flow cell 11.

[0072] The sealing neck 14b of the connecting piece 14 comprises an opening 25 having a receiving space 29 for receiving a flow line 15 (also referred to as a “capillary”, “inlet capillary” or “inlet line”), and also comprises a sleeve 30 having a clamping ring 31. The opening 25 is formed outside the flow cell 11 and has a receiving diameter d.sub.rec of approximately 1.6 mm in the embodiment shown here. The receiving space has a length of approximately 6 mm along the longitudinal axis A.sub.L.

[0073] The flow line 15, the diameter of which is minimally smaller than the receiving diameter d.sub.rec, is inserted completely into the receiving space 29 in the embodiment shown here. The flow line 15 is clamped in the receiving space via the sleeve 30 together with the clamping ring 31 and can thus be held in a stable position. In this way, a fluid-tight connection of the flow line 15 to the flow cell 11 via the connecting piece 14 is achieved. Since the flow line is only clamped, it can be easily removed from the connecting piece 14.

[0074] In the embodiment shown here, the sealing head 14a has an opening 27 through which the liquid NMR sample is conducted from the flow line 15 further into the flow cell 11. The opening 27 is located in the region 26 of the flow cell and the opening 26 has a transfer diameter d.sub.tran of approximately 0.8 mm. At the same time, the outer line 28a of the connecting line 28 is accessible via the opening 27. In the embodiment shown here, the transfer diameter d.sub.tran of the opening 27 is substantially equal to the outer line diameter d.sub.old (=0.8 mm) of the connecting line 28. In the embodiment shown here, an inner diameter of the flow line 15 is substantially equal to the transfer diameter d.sub.tran.

[0075] In the embodiment shown here, the flow line 15 is made of quartz glass, i.e., a rigid material. Furthermore, it is possible for the flow line 15 to be made entirely of a flexible material such as silicone, or for the flow line 15 to be made of a rigid material in the region of the connecting piece 14 and for the rest of the flow line 15 to be made of a flexible material.

[0076] FIG. 2 shows the schematic longitudinal section of the flow cell assembly 10 according to the invention from FIG. 1 with and without hatching to illustrate the flow spaces for a liquid NMR sample.

[0077] The flow cell 11 comprises a flow cell wall 11a (hatched area), which delimits an unfilled flow cell interior 11b (unhatched area) from its surroundings. In the embodiment shown here, the sealing head 14a of the connecting piece 14 is arranged in the flow cell interior 11b. The liquid NMR sample can be conducted in the remaining flow cell space.

[0078] The connecting piece 14 (hatched area) includes the connecting line 28, which is unfilled in the form shown here (unhatched area). In the embodiment shown here, the connecting line 28 is connected to the flow line 15. The flow line 15 comprises a line wall 15a (hatched area) which delimits an unfilled line interior 15b (unhatched area) from the surroundings and the connecting piece 14.

[0079] In an NMR measurement, the liquid NMR sample is conducted via the line interior 15b of the flow line 15 to the connecting line 28 of the connecting piece 14 and from there further into the flow cell interior 11b of the flow cell 11. The liquid NMR sample is then removed from the flow cell interior 11b at the second opening at the second end of the flow cell 11 (not shown in detail). However, the direction of flow can also run in the opposite direction from the second opening to the first opening 12 and then through the connecting piece 14 into a flow line 15.

[0080] FIG. 3 is a schematic view of a measurement setup for carrying out an NMR measurement of a liquid NMR sample 101 using an NMR spectrometer 100 and the flow cell assembly 10 according to the invention.

[0081] The NMR spectrometer 100 includes an NMR magnet arrangement 103 having a magnet bore 102, a sample holder 104, and an RF (=radio frequency) coil 105 for the excitation and detection of an NMR signal of the liquid NMR sample 101 and includes the flow cell assembly 10 according to the invention which is inserted into the sample holder 104 of the NMR spectrometer 100. The flow cell assembly 10 extends along the longitudinal axis A.sub.L and the magnet bore 102 extends along an axis A.sub.m; in the embodiment shown here, the longitudinal axis A.sub.L and the axis A.sub.m of the magnet bore 102 are substantially identical. In the embodiment shown here, an NMR magnetic field B.sub.0 is perpendicular to the longitudinal axis A.sub.L. However, in further embodiments not shown here, it is also possible for the NMR magnetic field B.sub.0 to be parallel to the longitudinal axis A.sub.L, for example.

[0082] The flow cell assembly 10 is connected to a first reservoir 106 via an inlet line 107, the inlet line 107 being connected to flow cell assembly 10 via the connecting piece. A pump 108 is connected to the inlet line 107. The flow cell assembly 10 is connected to a second reservoir 110 via an outflow line 109.

[0083] The liquid NMR sample 101 to be measured is located in the first reservoir 106. The liquid NMR sample 101 is fed to the flow cell assembly 10 via the inlet line 107 with the aid of the pump 108. From there, the liquid NMR sample is then fed into the second reservoir 110 via the outflow line 109.

Measurement of NMR Samples

[0084] The measurement of the NMR sample 101 using the NMR spectrometer 100 and the flow cell assembly 10 can be done in the following way:

[0085] The flow cell assembly 10 is assembled by inserting the connecting piece with the components described in FIG. 1 into the flow cell. The connecting piece and the flow cell form a positive fit at the first opening. The flow line, which is designed here as an inlet line 107, is connected to the connecting piece in a fluid-tight manner, it being possible for the liquid NMR sample 101 to be fed in via the inlet line 107. The outlet line 109 is attached to the second end of the flow cell.

[0086] The flow cell assembly 10 is inserted into the NMR spectrometer 100 that has the magnet bore 102 which comprises the sample holder 104 for the flow cell assembly 10. The magnet bore 102 is in turn arranged in an NMR magnet arrangement 103. Since the flow cell assembly 10, in a measuring zone of the flow cell 11, does not have any other components such as a flow line which could disrupt a magnetic field, it is substantially irrelevant in which direction the NMR magnetic field B.sub.0 generated by the NMR magnet arrangement 103 points. This means that the invention can be used both in NMR spectrometers 100 in which the magnetic field B.sub.0 is parallel to the magnet bore 102 (and thus parallel to the longitudinal axis A.sub.L of the flow cell) and in NMR spectrometers 100 in which the magnetic field B.sub.0 runs transversely to the magnet bore 102 (and thus transversely to the longitudinal axis A.sub.L of the flow cell).

[0087] After the flow cell assembly 10 is placed in the NMR spectrometer 100, the NMR measurement is started. The NMR measurement can be a single measurement or a continuous measurement, for example to follow a chemical reaction in real time.

[0088] During the NMR measurement, the liquid NMR sample 101 is conveyed from the first reservoir 106, with the aid of the pump 108, via the inlet line 107 to the connecting line. From the connecting line, the liquid NMR sample 101 flows into the flow cell and from there flows along the longitudinal axis A.sub.L to the outflow line 109 at the first opening of the flow cell. In the embodiment shown here, the liquid NMR sample 101 flows once through the flow cell in one direction. The liquid NMR sample 101 is then conducted from the flow cell into the second reservoir 110 via the outflow line 109.

[0089] After the NMR measurement is completed, the flow cell assembly 10 is removed from the sample holder 104 of the NMR spectrometer 100. The inlet line 107 is then removed from the connecting piece and the outflow line 108 is removed from the second end of the flow cell. The flow cell assembly 10 can then be cleaned, disassembled, or used for another NMR measurement.

[0090] The flow cell assembly 10 easily withstands pressures of up to 20 bar caused by the inflowing liquid NMR sample. At the same time, a good seal between the flow cell and the connecting piece is achieved, so that no liquid NMR sample 101 escapes from the flow cell assembly 10, thereby rendering the NMR measurement unusable or causing the NMR spectrometer 100 to be contaminated or damaged by the liquid NMR sample 101.

LIST OF REFERENCE SIGNS

[0091] 10 flow cell assembly [0092] 11 flow cell [0093] 11a flow cell wall [0094] 12b flow cell interior [0095] 12 first opening [0096] 13 first end [0097] 14 connecting piece [0098] 14a sealing head [0099] 14b sealing neck [0100] 15 flow line [0101] 15a line wall [0102] 15b line interior [0103] 16 outer contour [0104] 17 inner contour [0105] 18 region (of the first opening) [0106] 19 sealing element [0107] 19a sealing ring [0108] 20 inner wall [0109] 21 outer wall [0110] 22 region (of the sealing element) [0111] 23 annular peripheral groove [0112] 24 region (outside the flow cell) [0113] 25 opening (with receiving diameter d.sub.rec) [0114] 26 region (inside the flow cell) [0115] 27 opening (having transfer diameter d.sub.tran) [0116] 28 connecting line [0117] 28a outer line [0118] 28b inner line [0119] 29 receiving space [0120] 30 sleeve [0121] 31 clamping ring [0122] 100 NMR spectrometer [0123] 101 (liquid) NMR sample [0124] 102 magnet bore [0125] 103 NMR magnet assembly [0126] 104 sample holder [0127] 105 RF coil [0128] 106 first reservoir (for inflow) [0129] 107 inlet line [0130] 108 pump [0131] 109 outflow line [0132] 110 second reservoir (for outflow) [0133] A.sub.L longitudinal axis [0134] A.sub.m axis (of magnet bore) [0135] B.sub.0 NMR magnetic field [0136] d.sub.old outer line diameter [0137] d.sub.con connection diameter [0138] d.sub.rec receiving diameter [0139] d.sub.out outer diameter [0140] d.sub.seal sealing head diameter [0141] d.sub.fout flow cell outer diameter [0142] d.sub.lid inner line diameter [0143] d.sub.in inner flow cell diameter [0144] d.sub.op opening diameter [0145] d.sub.tran transfer diameter [0146] H.sub.c height (of the taper of the connecting piece) [0147] H.sub.f height (of the first opening)