Nuclear magnetic resonance spectroscopy, also referred to as NMR spectroscopy, is one of the most important and most meaningful methods for elucidating the structure of molecules. The investigations are predominantly effected in a condensed phase, that is to say in solution or in the solid state. The advantage of this method over other methods is that it is possible to obtain statements about the structure of molecules even in multicomponent systems, without requiring a priori knowledge of the constituents. For elucidating the structure of chemical compounds, use is often also made of combined methods, that is to say methods in which firstly a multicomponent system is separated into the individual components before the individual components are then analyzed separately. One example of such an integrated system is gas chromatography mass spectroscopy (GC-MS), by means of which substances can be detected and analyzed even in the nanograms range. However, mass spectroscopy yields only limited information about the structure of a chemical compound. Moreover, this method has the disadvantage that the sample is destroyed by the investigation, which is problematic precisely in the case of samples which are particularly valuable or are present only in extremely small amounts. NMR spectroscopy does not have this disadvantage, by contrast, since the sample is not destroyed during the NMR-spectroscopic investigation. Therefore, analysis methods are desirable in which a separation system, such as, for example, capillary electrophoresis or liquid chromatography, is combined with NMR spectroscopy in an integrated system.
However, the inherent insensitivity of the NMR method has limited its usability as a detection method, for a liquid phase analysis of very small samples. Thus, only microgram amounts of a substance can be routinely examined with commercially available NMR spectrometers, small sample tubes having a diameter of 5 mm and a solution volume of approximately 500 μl being used in such an application. Amounts in the micrograms range, on the other hand, can only be examined in extremely lengthy measurements and with diminished small sample tubes (1 mm) and solution volume (1 μl). Even smaller sample volumes are difficult to realize, however, which impedes an application in conjunction with capillary electrophoresis or liquid chromatography. Such a method would be desirable, however, precisely with regard to chemical synthesis and biotechnology, which require an efficient analysis of samples in the high throughput range.
The problem of the low sensitivity can be solved, however, by the use of miniaturized detection coils in the NMR measuring device. By means of smaller coils, it is possible to significantly improve the sensitivity compared with conventional coils. A critical quantity in the assessment of the sensitivity of a measurement is the signal/noise ratio (S/N). The latter is proportional to the sample volume VP and to the strength of the radiofrequency field B1. Moreover, S/N is inversely proportional to the root of the resistance of the detection coil R. Since R is proportional to the coil radius rs, the following holds true:S/N˜VP·B1/rs1/2
Consequently, the signal/noise ratio can be maximized by reducing the coil diameter. In order, however, to obtain a satisfactory signal in the case of a reduced coil radius, the coil internal diameter would have to be matched as well as possible to the sample size.
DE 199 27 976 A1, which is hereby incorporated by reference in its entirety, describes, for a use in a liquid phase analysis, a miniaturized overall analysis system having an NMR detection compartment around which an RF microcoil is situated. However, when using the arrangement described in DE 199 27 976 A1, the correspondence between the size of the sample and the size of the NMR detection coil is not optimal, as a result of which the sensitivity of the NMR-spectroscopic measurement is restricted.