Abstract:
There is providesd a nuclear magnetic resonance spectrometer having a high sensitiveness by simultaneously realizing a high uniformity of a static magnetic field and a high measuring sensitiveness. A sample tube used in the nuclear magnetic resonance spectrometer is constructed in a structure in which the shape of a sample placed in a measuring space can be changed. The change in shape of the sample can be achieved by controlling the pressure applied to the sample. There is at least one surface of contact between the sample placed in the measuring space and a gas existing around the sample, and the shape of such surface is maintained by the surface tension of the sample. In this case, a central portion of a magnet, into which the sample tube is inserted, filled with a sterilizing gas having a pressure higher than the atmospheric pressure, and the sample having a surface of contact with the gas is maintained in a sterile state. A measuring coil used in the nuclear magnetic resonance spectrometer is disposed on a rotatable curved surface symmetrical with respect to a rotational axis provided by a longitudinal center axis of the sample tube.

Description:
BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The present invention relates to a nuclear magnetic resonance spectrometer using a sample tube for a sample whose shape is deformable, and a method for operation thereof. 
     2. Description of the Related Art 
     The shapes of a sample tube and a detection coil in a nuclear magnetic resonance spectrometer (which will be referred to as a NMR system hereinafter) as shown in  FIG. 2  are well-known. For example, a sample tube shown in  FIG. 2  in JP-A-06-249934 has a shape similar to that of a common test tube, and in measuring thereof, the sample tube is inserted into a central portion of a NMR magnet adapted to generate an intense static magnetic field. 
     A housing  12  of a detecting device (probe) and a measuring coil  14  are disposed around the inserted sample tube  10  to surround the sample tube  10 . A gas  15  is also present between the sample tube  10  and the housing  12  of the detecting device. In general, a sample solution  18 , the sample tube  10  and the gas  16  are different in magnetic permeability from one another, and hence, a boundary surface perpendicular to the static magnetic field is magnetized to disturb the static magnetic field around the boundary surface. 
     For example, when the static magnetic field generated by the magnet faces in an axial direction of the sample tube  3 , the static magnetic field is disturbed at vertically opposite ends of the sample solution  18  and the sample solution  20 , i.e., at portions outside the boundary. In order to reduce the adverse affection exerted to an NMR spectrum by the disturbance of the static magnetic field, only a signal transmitted from a sample portion  18  of the sample solutions  18  and  20  filling the sample tube  10 , which is present at a central portion where the static magnetic field is not disturbed, is detected by the measuring coil  14 . The signal emitted from that portion of the sample solution  20  exists outside a space surrounded by the coil  14  and cannot reach the measuring coil  14 , because of a low sensitiveness of the measuring coil  14 . 
     In the system shown in  FIG. 2  and described in JP-A-06-249934, the uniformity of the static magnetic field is poor, and in order to prevent the degradation of the NMR spectrum due to the disturbance of the static magnetic field, a surplus sample  20  to be measured is required in addition to the sample solution  18  to be measured, which makes it difficult to analyze a very small amount of a sample. In order to improve the problem associated with JP-A-06-249934, JP-A-05-249214 has been proposed. A system described in this JP-A-05-249214 includes a spherical (in general, elliptic) measuring space into which a sample solution  18  to be measured is placed, and a capillary tube  22  for introduction of a sample solution into the measuring space, as shown in  FIG. 3 . 
     According to JP-A-05-249214, the shape of the sample solution is spherical or elliptic, and in the static magnetic field which is uniform spatially, the static magnetic field in the sample solution can be uniformized irrespective of the sample solution  18  and the magnetic permeability of the sample tube  10  and the peripheral gas  16 . This is because a difference in permeability between inside and outside the ellipse disturbs the magnetic field around the sample solution  18 , but does not disturb the internal magnetic field in the sample solution  18 , according to an electro-magnetological law. Therefore, in the system described in JP-A-05-249214, the uniformity of the static magnetic field can be enhanced by forming the sample solution into the elliptic shape. However, as can be seen from the geometrical dispositions of the sample tube  10  and the measuring coil  14  as shown in  FIG. 3 , the distance between the measuring coil  14  and the sample solution  18  is larger, and the measuring sensitivity is lower. 
     SUMMARY OF THE INVENTION 
     Accordingly, it is an object of the present invention to provide an NMR system having a high sensitiveness by simultaneously realizing a high uniformity of a static magnetic field and a high measuring sensitiveness. 
     To achieve the above object, according to the present invention, there is provided a nuclear magnetic resonance spectrometer, comprising a probe having an elliptic or spherical measuring space, a sample tube having a capillary tube extending into the measuring space through an insertion opening provided in the probe, a signal-detecting coil disposed along an elliptic or spherical portion of said probe outside the measuring space, wherein a sample is pushed into the measuring space through the capillary tube and maintained in an elliptic or spherical shape in the measuring space by a surface tension of the sample. 
     With the above arrangement, by deforming the sample into an elliptic shape after insertion of the sample into the measuring coil, the sample can be positioned in the space in which the static magnetic field created by a magnet is more uniform, and the disturbance of the static magnetic field due to the sample can be prevented. Thus, the uniformity of the static magnetic field applied to the sample can be enhanced, thereby providing an NMR spectrum having a high resolution and a high sensitiveness. 
     Other objects, features and advantages of the invention will become apparent from the following description of the embodiments of the invention taken in conjunction with the accompanying drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a sectional plan view of a sample tube and a measuring coil according to the present invention; 
         FIG. 2  is a sectional plan view of a sample tube and a measuring coil described in JP-A-06-249934; 
         FIG. 3  is a sectional plan view of a sample tube and a measuring coil described in JP-A-05-249214; 
         FIG. 4  is a sectional plan view of the sample tube according to the present invention; 
         FIG. 5  is a sectional plan view of a portion of an NMR system to which the present invention is applied; 
         FIG. 6  is a sectional plan view of a tip end of a probe including the sample tube and the measuring coil according to the present invention mounted therein; 
         FIGS. 7A to 7E  are flow diagrams showing operations carried out using the sample tube according to the present invention; 
         FIG. 8  is a plan view of the shapes of a portion of the sample tube according to the present invention and a sample to be measured; 
         FIG. 9  is a plan view of a sample tube and a measuring coil according to another embodiment of the present invention in section; 
         FIG. 10  is a sectional plan view of a sample tube and a measuring coil according to a further embodiment of the present invention. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     The present invention has been accomplished by attaining an object for simultaneously realizing a high uniformity of static magnetic field and a high measuring sensitiveness by changing the shape of a sample after insertion of the sample into a measuring coil.  FIG. 1  shows a sample tube for NMR and a measuring coil according to one embodiment of the present invention. 
     A sample tube body  10  for containing a sample  18  to be measured and a non-measured sample  20  has a capillary tube  22  at its lower portion. A support plate  24   a  is provided around an outer periphery of an opening of the capillary tube  22 . A support plate  24   b  is mounted in an opposed relation to the support plate  24   a , so that the distance between the support plates  24   a  and  24   b  can be regulated by vertically moving a support shaft  26  supporting the support plate  24   b . Each of the support plates  24   a  and  24   b  is made of a material having a small wettability to the sample  18 . 
     The sample  18  to be measured is pushed out of a lower portion of the capillary tube  22  and brought into direct contact with a peripheral gas  16 . The shape of the contact surface of the sample  18  is maintained by the surface tension of the sample  18 , as will be described hereinafter. The peripheral gas  16  is a sterilizing gas having a pressure higher than the atmospheric pressure. The face of the sample  18  which is not in contact with the peripheral gas  16  is in contact with the two support plates  24   a  and  24   b . The shape and volume of the sample  18  to be measured can be controlled by changing the distance between the support plates  24   a  and  24   b.    
     The sample tube body  10  and the capillary tube  22 , the support plates  24   a  and  24   b  mounted in the opposed relation to each other and the support shaft  26  are contained within a probe container  12 . The probe container  12  has a spherical portion  28 , within which the sample  18  pushed out of the capillary tube  22  is formed into a spherical elliptic shape by the surface tension. 
     One  24   a  of the two support plates  24   a  and  24   b , which is located at a tip end of the sample tube body  10 , has a single hole  30  or a plurality of holes  30  connected to the capillary tube  22 . The capillary tube  22  acts as a passage connecting the sample to be measured  18  and the non-measured  20  contained in the sample tube body  10  to each other. 
     The support plate  24   b  spaced apart from the sample tube body  10  is coupled to the support shaft  26  and used to control the shape and volume of the sample  18  to be measured. The support shaft  26  is vertically movably supported. 
     The probe  12  is disposed to surround the sample  18  to be measured and the peripheral gas  16 , and a space within the probe, in which the measuring coil  14  and other electric circuits are actually mounted, is protected from the entrance of the sample and the gas. The measuring coil  14  is disposed on a rotatable curved surface symmetrical with respect to a rotational axis provided by a longitudinal center axis of the sample tube body  10 . The measuring coil  14  is also mounted along outside the spherical portion of the probe  12  and hence, in order to ensure that the measuring coil  14  extends along the contour of the sample  18  formed into the spherical shape, the distance between the measuring coil  14  and the surface of the sample  18  is substantially uniform and small. 
     As shown in detail in  FIG. 4 , the sample tube body  10  is thinner at its tip end provided with the capillary tube  22 , and the sample support plate  24   a  formed into a collar shape is mounted at a tip end of the capillary tube  22 . The support plate  24   b  opposed to the support plate  24   a  is capable of being brought into contact with the support plate  24   a  so as to close a hole  8   c  in the support plate  24   a  connected to the capillary tube  22 . A groove  32  of a nut for connection with the support shaft  26  is formed in a face of the support plate  24   b  opposite from a face coupled to the support plate  24   a . The control of the internal pressure in the sample tube  10  is carried out by controlling the movement of a piston  34  mounted within the sample tube  10 . 
       FIG. 5  shows an embodiment of the present invention applied to an NMR system using a split-type magnet. In the split-type magnet, a magnet  36  is comprised of two or more separated magnet units  38 ,  40 ,  42  and  44 . A probe  46  is inserted into a bore  48  provided in a central portion of the magnet  36 , and a pressure transmitting pipe  52  connected to a pressure controller  50  and a support shaft  26  connected to a support shaft position controller  54  are connected to a tip end of the probe  46 . 
       FIG. 6  shows a sample insertion bore and a measuring coil at the tip end of the probe. The split-type magnet is shown in  FIG. 5 , but a solenoid-type magnet is used in this embodiment.  FIG. 5  shows the probe having a sample insertion bore perpendicular to an axis of a probe housing, but a probe having a sample insertion bore parallel to an axis of probe housing is used in this embodiment. 
       FIGS. 7A to 7D  are flow diagrams for explaining operations when a sample tube according to the present invention is used for NMR measurement.  FIGS. 7A to 7D  correspond to steps A to D shown in  FIG. 7E , respectively. When the sample tube  3  is inserted from above, the support plate  24   a  located at a tip end of the sample tube  3  is stopped at a location corresponding to an inlet of a hole formed at one end of a spherical or elliptic space (step A and  FIG. 7A ). 
     When the sample tube  3  has been stopped, the support shaft  26  is raised, whereby the support plate  24   b  is brought into contact with and coupled to the support plate  24   a . In this case, the movement of the support shaft  26  is controlled by the support shaft position controller  54  shown in  FIG. 5  (step B and  FIG. 7B ). When the coupling of the support plate  24   b  to the support plate  24   a  has been completed, the pressure controller  12  shown in  FIG. 5  lowers the piston  18  shown in  FIG. 4  through the pressure transmitting pipe  13  to increase the internal pressure in the non-measured sample  20  located in the sample tube body  10 . 
     At the same time, the support shaft  26  is lowered. The increase in internal pressure and the lowering of the support shaft  26  cause the support plate  24   b  to be moved away from the support plate  24   a , whereby the sample  18  to be measured emerges from the capillary tube  22  between the support plates  24   a  and  24   b  (step C and  FIG. 7C ). When the volume of the sample  18  to be measured reaches a target value, the pressure in the sample tube and the position of the support shaft  26  are kept constant, and the measurement is started (step D and  FIG. 7D ). 
     The shape of the contact face between the sample  18  to be measured and the peripheral gas  16  at the steps C and D in  FIG. 7E , if no force other than the surface tension is applied, is determined according to the following Laplace formulae (1) and (2): 
                       P   1     -     P   2       =     α   ⁡     (       1     R   1       +     1     R   2         )               (   1   )                 Δ   ⁢           ⁢   P     =       P   1     -     P   2               (   2   )               
which are referred to the document, L. D. Landau and E. M. Lifshitz, “FLUID MECHANICS”, 2nd English Edition (Pergamon, 1986).
 
     In the above formulae, P 1  and P 2  are internal pressures in the sample  18  to be measured and the peripheral gas  16 , respectively; α is a coefficient of surface pressure; and ΔP represents a difference in pressure on the contact surface. To ensure that the contact surface is stable, it is a necessary and sufficient that ΔP has the same value at all points on the contact surface. 
     In addition, R 1  and R 2  are a magnitude called a principal radii of curvature in geometry, and (1/R 1 +1/ R 2 ) is defined as a mean curvature and used to describe the shape of a three-dimensional curved surface. According to a differential geometry, when all points (x, y, z) on the three-dimensional curved surface satisfy an equation, F(x, y, z))=0, the mean curvature is represented by the following equation (3): 
     
       
         
           
             
               
                 
                   
                     
                       
                         
                           
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     If the equation (3) is replaced into the equation (1), an equation (4) is provided, and a function F(x, y, z) representing the stable shape of the contact surface can be determined by the internal pressures P 1  and P 2  and the coefficient α of surface tension (for example, see Document: C. Pozrikidis, “Introduction to Theoretical and Computational Fluid Dynamics”, Oxford University Press, New York, 1997). 
     
       
         
           
             
               
                 
                   
                     
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     If the presence of a force other than the surface tension must be taken into consideration, then it is added as another term to a right side of the equation (4). For example, if the influence of the force of gravity applied in a z-direction is taken into consideration, the equation is changed to the following equation: 
     
       
         
           
             
               
                 
                   
                     
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     In the equation (5), g, ρ 1  and ρ 2  are a gravitational acceleration constant, a density of the sample  18  and a density of the peripheral gas  16 , respectively. One example of a shape of the sample to be measured  18  determined by the surface tension and the force of gravity given in equation (5) is shown in  FIG. 8 . 
     In the equation (5), P 1  is a pressure of the sample to be measured  18  shown in  FIG. 1 . According to Pascal&#39;s principle, the pressure of the sample  18  to be measured is equal in a steady state to the pressure of the non-measured sample  20  connected to the capillary tube  22  and can be controlled easily by regulating the pressure of the non-measured sample  20 . 
     In contrast to this case, g, ρ 1 , ρ 2  and α are determined by a place where the NMR measurement is carried out and the sample and gas used. Therefore, a range capable of being selected for each of g, ρ 1 , ρ 2  and α is very narrow, and it is difficult to use them as control factors. The pressure P 2  of the peripheral gas  16  is not appropriate as a control factor, because of the characteristic of the NMR system in which the peripheral gas  16  is always circulated by a tube outside the magnet. Therefore, in the embodiment of the present invention, the shape of the sample  18  to be measured is changed by controlling the pressure applied to the non-measured sample  20 . 
     By constructing the sample tube and the measuring coil of the NMR system as described in the above-described first embodiment, the shape of the sample can be changed to an elliptic shape after insertion of the sample into the measuring coil. Further, the sample is positioned in a more uniform space by the static magnetic field created by the magnet, and the uniformity of the static magnetic field applied to the sample is enhanced by preventing the disturbance of the static magnetic field due to the sample, leading to improvements in resolution and sensitiveness of an NMR spectrum. In addition, the measuring coil can be disposed along the surface of the ellipse without prolongation of the distance between the sample and the measuring coil, leading to a further enhancement in measuring sensitiveness. 
       FIG. 9  shows another embodiment of the present invention. In this embodiment, a sample  18  to be measured is placed in contact with a support plate  24   a  which is connected to a capillary tube  22  provided at a tip end of a sample tube body  10 .  FIG. 9  shows an example in which the sample  18  to be measured is positioned above the support plate  24   a , but the support plate  24   a  may be disposed above the sample  19  to be measured, or may be at another location. Other portions and components shown in  FIG. 9  are similar to those in the first embodiment and hence, the description of them is omitted. 
     In the second embodiment, a support plate  24   b  and a support shaft  26  connected to the support plate  24   b  as well as a support shaft position controller  14  are eliminated and hence, the arrangement and operation are simple, as compared with those in the first embodiment. Therefore, if a sample tube and a measuring coil of the NMR system are constructed as in the second embodiment, the same effect as in the first embodiment can be likewise obtained in the simple arrangement. In addition, an upper portion of a housing  12  is opened and hence, it is possible to project light or a laser beam for the measurement and to insert a pipette. 
     However, the arrangement in the second embodiment includes no support plate  24   b  and hence, the volume of the sample  18  to be measured whose shape can be maintained stably is decreased as compared with that in the first embodiment, and the intensity of a signal measured is decreased in accordance with the decrease in volume of the sample to be measured. 
       FIG. 10  shows a further embodiment of the present invention. In this third embodiment, an elastic container  56  made of an elastomeric material containing no hydrogen is disposed between a sample  18  to be measured and a peripheral gas  16 , unlike the above-described first and second embodiments. The use of the elastic container  56  of the material containing no hydrogen ensures that the volume of the sample  18  to be measured, whose shape can be maintained stably, can be increased without deterioration of the simplicity of the arrangement and operation of the system in the second embodiment. 
     It should be further understood by those skilled in the art that although the foregoing description has been made on embodiments of the invention, the invention is not limited thereto and various changes and modifications may be made without departing from the spirit of the invention and the scope of the appended claims.