JPS6119934B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a nuclear magnetic resonance apparatus, and more particularly to a nuclear magnetic resonance apparatus having an improved magnetic field control system.

An atomic nucleus has a magnetic moment, and when placed in a magnetic field oriented in a certain direction, polarization occurs in the direction of the magnetic field. When a high-frequency magnetic field is applied perpendicularly to this polarizing magnetic field, the magnetic moment of the atomic nucleus causes a precession movement around the direction of the polarizing magnetic field, causing rotation of the magnetic moment with the same angular velocity as the applied high frequency. It becomes like this. This is what is called nuclear magnetic resonance. If the frequency of the given high frequency is f, the magnetic field strength is H, σ is the shielding coefficient that varies depending on the position of the nucleus to be measured in the molecule in the sample to be measured, and γ is the gyromagnetic ratio of the nucleus to be measured, then the nucleus It is well known that the magnetic resonance condition is given by f=γ(1-σ)H, and the main purpose of a nuclear magnetic resonance apparatus is to understand the difference in σ in this equation depending on the molecular structure.

Nuclear magnetic resonance instruments have extremely high resolution, but require extremely highly stabilized magnetic fields. For this purpose, magnetic field control is performed in nuclear magnetic resonance apparatuses, and a method generally used is to excite resonance of a reference nucleus and control the magnetic field based on the resonance signal. There are two types of this method. One is the so-called external lock method, which uses a resonance signal from a reference nucleus in a reference sample independent of the sample to be measured as the resonance signal of the reference nucleus, and the other uses the resonance signal of the reference nucleus to be measured as the resonance signal of the reference nucleus. This is a so-called internal lock method that uses a resonance signal from a reference nucleus contained in a sample.

In the external lock method, the reference sample is placed independently of the sample to be measured, so a reference sample with a wide bandwidth of the resonance signal used for magnetic field control can be selected and used regardless of the sample to be measured. Although it has the advantages of fast response to interfering magnetic fields (response time is inversely proportional to bandwidth), and the frequency range that can be pulled into the magnetic field control state is sufficiently wide, the pulling operation is easy.
Since the two samples are located at different positions, there is a problem in that the slight difference in magnetic field strength between the two positions (ie, magnetic field deviation) and its temporal fluctuation hinder accurate measurement of chemical shift. On the other hand, the internal lock method has the problems of the external lock method as advantages, and the advantages as problems.

The present invention has been made in view of these points, and its purpose is to provide a nuclear magnetic resonance apparatus that utilizes the above-mentioned good aspects of the external lock method and improves on the bad aspects.

According to the present invention, magnetic field control by the external lock method is used, and therefore the inherent advantages of the external lock method as described above are still provided. Further, the resonance signal for magnetic field control by the internal lock method is used to change the resonance conditions of the magnetic field control system of the external lock method so as to compensate for the magnetic field deviation between the two sample positions in the external lock method. This solves the problems described above with the external lock method.

FIG. 1 shows in block diagram form one embodiment of a nuclear magnetic resonance apparatus according to the present invention. In FIG. 1, a sample to be measured 2 and a reference sample 3 are placed at different positions in a unidirectional spatial magnetic field generated by a magnet device 1. The sample to be measured 2 includes a nucleus to be measured and a reference nucleus, and the reference sample 3 includes a reference nucleus. Transmitting coils 4 and 5 and receiving coils 6 and 7 are wound around the sample to be measured 2 and the reference sample 3, respectively, and the oscillating coils 4 and 5 are connected to high frequency oscillators 8 and 9, respectively. Modulation coils 10 and 11 are further arranged in the magnetic field to respectively modulate the magnetic field of the space in which the sample to be measured 2 and the reference sample 3 are arranged, and the magnet device 1
It also includes a magnetic field coil 12 for controlling the magnetic field. The receiving coil 6 includes a high frequency amplifier 13, a high frequency detector 14 to which the high frequency from the high frequency oscillator 8 is given as a reference signal, an audio frequency amplifier 15,
A phase detector 16 and a recorder 17 are connected in sequence. A high frequency amplifier 18, a high frequency detector 19 to which the high frequency from the high frequency oscillator 9 is given as a reference signal, an audio frequency amplifier 20, a phase detector 21, and a magnetic field control circuit 22 are sequentially connected to the receiving coil. It is connected to the magnetic field control coil 12. An audio frequency oscillator 23 is connected to the modulation coil 11, and the audio frequency oscillator supplies an audio frequency as a reference signal to the phase detector 21 via a phase shift circuit 24. An audio frequency amplifier 25, a phase detector 26, and a frequency control circuit 27 are further connected in sequence to the high frequency detector 14, and the frequency control circuit controls the audio frequency generated by the audio frequency oscillator 23 by its output. I'm starting to do that. Audio frequency oscillators 29 and 30 are connected to the modulation coil 10 via an adder 28, and the audio frequency oscillators provide audio frequencies as reference signals to phase detectors 16 and 26 via phase shift circuits 31 and 32, respectively. It's becoming like that. When the horizontal axis of the recording chart of the recorder 17 is the feeding direction of the chart, a voltage proportional to the horizontal axis voltage controls the audio frequency generated by the audio frequency oscillators 30 and 23. It's summery. Therefore, the audio frequency generated by the audio frequency oscillator 23 is controlled by the sum of the output of the frequency control circuit 27 and the voltage proportional to the horizontal axis voltage of the recorder 17.

In the above configuration, the high frequency f _R from the high frequency oscillator 8 is applied to the sample under test 2 through the oscillation coil 4, and the audio frequency fm ₁ from the audio frequency oscillator 29 is applied to the modulating coil 10 via the adder 28. When the magnetic field of the space in which the sample to be measured 2 is placed is modulated by giving , the receiving coil 6 can detect a resonance signal that satisfies the following resonance condition.

f _R + fm ₁ = γ (1 - σ ₁ ) H ₀ ... (1) However, Ho is the magnetic field strength of the space where the sample to be measured 2 is placed, and γ is the magnetic rotation of the nucleus to be measured in the sample to be measured 2 A constant called a ratio σ ₁ is a shielding coefficient that takes a different value depending on the position that the nuclei to be measured in the sample 2 to be measured occupy within the molecules of the sample.

When the resonance condition of equation (1) is satisfied, the reception coil 6 detects a resonance signal of f _R +fm ₁ . This signal is amplified by the high frequency amplifier 13, then detected by the high frequency detector 14 using the high frequency f _R as a reference signal, and converted into a signal of _fm1 .
This fm ₁ signal is amplified by the audio frequency amplifier 15 and then detected by the phase detector 16 using the audio frequency fm ₁ from the audio frequency oscillator 29 as a reference signal. In this case, if the phase of the audio frequency fm ₁ as the reference signal is appropriately determined by the phase shift circuit 31, an absorption waveform signal can be extracted from the phase detector 16.

On the other hand, the high frequency f _R3 from the high frequency oscillator 9 is applied to the reference sample 3 through the oscillation coil 5, and the audio frequency fm ₃ from the audio frequency oscillator 23 is applied to the modulating coil 11.
When the magnetic field of the space in which the reference sample 3 is placed is modulated by giving , a resonance signal that satisfies the following resonance condition can be detected by the receiving coil 7.

f _R3 + fm ₃ = γ ₃ (1-σ ₃ ) H ₀ '...(2) However, H ₀ ' is the magnetic field strength of the space where the reference sample 3 is placed, and γ ₃ is the intensity of the reference nucleus in the reference sample 3. The gyromagnetic ratio, σ ₃ , is a shielding coefficient that takes a different value depending on the position that the reference nucleus in the reference sample 3 occupies within the molecule in the sample.

When the resonance condition of equation (2) is satisfied, the reception coil 7 detects a resonance signal of f _R3 +fm ₃ . After this signal is amplified by the high frequency amplifier 18, it is detected by the high frequency detector 19 using the high frequency f _R3 as a reference signal, and is converted into a signal of _fm3 .
This _fm3 signal is amplified by the audio frequency amplifier 20, and then detected by the phase detector 21 using the audio frequency _fm3 from the audio frequency oscillator 23 as a reference signal. In this case, if the phase of the audio frequency fm ₃ as the reference signal is appropriately determined by the phase shift circuit 24, a signal with a dispersion waveform can be extracted from the phase detector 21. By controlling the current flowing through the magnetic field control coil 12 using the magnetic field control circuit 22 using this signal, the magnetic field in the space where the reference sample 3 is placed is controlled so as to always satisfy equation (2).
can be maintained at Ho′. Furthermore, if the audio frequency fm ₃ of the audio frequency oscillator 23 is swept by a voltage proportional to the horizontal axis voltage of the recorder 17, Ho' will change accurately by an amount corresponding to the amount of change in this fm ₃ . Since the sample to be measured 2 is placed very close to the reference sample 3, the magnetic fields Ho and Ho' at both sample positions are almost equal, so the chemical shift in the sample to be measured 2 changes depending on the change in Ho'. The recorder 17 can record spectra of resonance lines of each different nucleus.

The above explanation is about a nuclear magnetic resonance apparatus using the well-known external lock method, but in FIG.
through adder 28 and modulation coil 10
It is modulated by an audio frequency called fm ₂ . Therefore, the reception coil 6 also detects resonance signals that satisfy the following resonance conditions.

f _R + fm ₂ = γ (1 - σ ₂ ) H ₀ ...(3) However, γ is the gyromagnetic ratio of the reference nucleus in the sample to be measured 2, and σ ₂ is the gyromagnetic ratio of the reference nucleus in the molecule in the sample. This is a shielding coefficient that takes different values depending on the location occupied. The reference nucleus in the sample to be measured 2 may be the same type of nucleus as the nucleus to be measured or may be a different type of nucleus, but in the embodiment shown in FIG. 1, the reference nucleus in the sample to be measured 2 is This was assumed to be the nucleus to be measured. This is why γ is the same in equations (1) and (3).

When the resonance condition of equation (3) is satisfied, the resonance signal f _R +fm ₂ detected by the receiving coil 6 is amplified by the high frequency amplifier 13, and then the high frequency f _R is detected by the high frequency detector 14. It is detected as a reference signal and converted to an fm ₂ signal. This fm ₂ signal is amplified by the audio frequency amplifier 25 and then detected by the phase detector 26 using the audio frequency fm ₂ from the audio frequency oscillator 30 as a reference signal. In this case, if the phase of the audio frequency fm ₂ as the reference signal is appropriately determined by the phase shift circuit 32,
A dispersion waveform signal representing a differential waveform of the absorption waveform can be extracted from the phase detector 26. This signal is applied to a frequency control circuit 27, which controls the audio frequency _fm3 of the audio frequency oscillator 23 in accordance with the magnitude of the dispersion waveform signal that is an input signal thereto. Therefore, the audio frequency fm ₃ of the audio frequency oscillator 23 is controlled by the sum of the voltage proportional to the horizontal axis voltage of the recorder 17 and the output voltage of the frequency control circuit 27. If this sum is fm ₃ +Δf, the resonance conditional expression (2) for the reference sample 3 can be rewritten as follows.

f _R3 +fm ₃ +△f=γ ₃ (1-σ ₃ ) Ho (4) where △f is the change in fm ₃ caused by the frequency control circuit 27.

The following equation can be obtained from equations (1) and (3).

fm ₂ −fm ₁ = γHo(σ ₁ −σ ₂ ) ...(5) Therefore, if resonance satisfying equation (1) is observed while satisfying the resonance condition of equation (3), then By reading the difference between fm ₁ and fm ₂ using a counter or the like in the conventional manner, the chemical shift can be accurately measured in exactly the same way as in a nuclear magnetic resonance apparatus using the conventional internal lock method.

On the other hand, in FIG. 1, not only the audio frequency fm ₃ of the audio frequency oscillator 23 but also the audio frequency fm 2 of the audio frequency oscillator ₃₀ is swept by a voltage proportional to the horizontal axis voltage of the recorder 17. As a result, it is assumed that the following relational expression is satisfied in the relationship between equations (3) and (4).

f _R3 /f _R = fm ₃ / fm ₂ = γ ₃ (1-σ ₃ )/
γ(1−σ ₂ )……(6) Here, assuming the deviation between the magnetic field of the space where the measurement sample 2 is placed and the magnetic field of the space where the reference sample 3 is placed as △H, Ho′=Ho+△ By substituting H into equation (4), the following equation can be obtained.

f _R3 +fm ₃ +△f=γ ₃ (1-σ ₃ )Ho +γ ₃ (1-σ ₃ )△H ...(7) Furthermore, fm ₂ and
Since a sweep of fm ₃ is performed, substituting equation (6) into equation (7) yields the following.

Δf=γ ₃ (1−σ ₃ )ΔH (8) That is, the audio frequency fm 3 of the audio frequency oscillator 23 controlled through the frequency control circuit 27 by the resonance signal of the reference nucleus in the sample ₂ to be measured. The deviation ΔH between Ho' and Ho is corrected by the change Δf.

In FIG. 1, a reference sample 3, a high frequency oscillator 9, an oscillating coil 5, a receiving coil 7, a modulating coil 1
1, audio frequency oscillator 23, phase shift circuit 24,
High frequency amplifier 18, high frequency detector 19, audio frequency amplifier 20, phase detector 21, magnetic field control circuit 22
The system consisting of the magnetic field control coil 12 and the magnetic field control coil 12 is a so-called external magnetic field control system. The inherent advantages of the external lock method are therefore retained. In addition, fm ₃ is controlled by the resonance signal of the reference nucleus in the sample to be measured 2, and not only fm 3 but also fm ₃ is controlled by a voltage proportional to the horizontal axis voltage of the recorder 17.
Since fm ₂ is also swept, the above system also performs the function of the so-called internal lock method, and therefore, as is clear from the above explanation, the magnetic field deviation between the two sample positions in the external lock method is The problem will be resolved.

In Fig. 1, an example is shown in which fm ₃ is controlled by the frequency control circuit 27, but the same effect can be obtained by controlling f _R3 instead of fm ₃ as shown in equation (4). It is clear from the relationship. In this case, the output of the frequency control circuit 27 that has been applied to the audio frequency oscillator 23 will be applied to the high frequency oscillator 9.

FIG. 1 also shows an example in which the magnetic field is swept along with the horizontal axis sweep of the recorder 17, thereby obtaining the resonance spectrum of the nucleus to be measured _. There is a so-called frequency sweep method in which a resonance spectrum is obtained by sweeping, and the present invention is also applicable to this method. In this case, fm ₂ and fm ₃ are stopped from being swept by a voltage proportional to the sweep voltage of the recorder 17, and fm ₂ is fixed, and fm ₃ is controlled only by the output of the frequency control circuit 27. and sweep fm ₁ by a voltage proportional to the horizontal axis sweep voltage, thus controlling the magnetic field by the resonance of the reference nucleus in the reference sample 3 and the magnetic field in the sample to be measured 3. The combination of frequency control of fm ₃ by the resonance of the reference nucleus keeps the magnetic field constant, and in that state an accurate resonance spectrum can be measured by sweeping fm ₁ .

The frequency sweep method includes a high frequency sweep method in which f _R is swept without changing fm ₁ , and the present invention is also applicable to this method. In this case, under the resonance conditions of equations (1) and (3), set f _R and fm ₂ to be equal in sweep width and opposite in sign so that f _R + fm ₂ = constant relationship is maintained. It sweeps in proportion to the horizontal axis voltage, and fm ₁ is fixed. In this way, the resonance condition in equation (3) remains the same as when fm ₁ is swept, and the resonance condition in equation (1) is changed to the point where f _R is swept instead of fm ₁ . It is clear that the effect is exactly the same as when sweeping fm ₁ , except for the difference. In this method, a voltage proportional to the horizontal axis voltage of the recorder 17 is applied to the high frequency oscillator 8 and the audio frequency oscillator 30, and the respective frequencies are swept in opposite directions by the same magnitude. Of course, fm ₁ is fixed, and fm ₃ of the audio frequency detector 23 is controlled by the output of the frequency control circuit 27.

As is clear from the above description, according to the present invention, the above-mentioned objects of the present invention are completely achieved, and the practical effects thereof are enormous.

[Brief explanation of the drawing]

FIG. 1 is a block diagram of a nuclear magnetic resonance apparatus showing one embodiment of the present invention. Explanation of symbols, 2, 3... Sample, 8, 9... High frequency oscillator, 14, 19... High frequency detector, 16,
26, 21... Phase detector, 29, 30, 23...
...Audio frequency oscillator, 17...Recorder, 27...Frequency control circuit, 12...Magnetic field control coil.

Claims (1)

[Claims] 1. Means for arranging a sample to be measured including a nucleus to be measured and a reference nucleus at a first position in a magnetic field, means for arranging a reference sample including a reference nucleus at a second position in the magnetic field, and a magnetic field control thread including means for exciting and measuring nuclear resonance; and means for exciting resonance of a reference nucleus in the reference sample and controlling the magnetic field based on the resonance signal; and the sample to be measured. means for exciting the resonance of a reference nucleus in the magnetic field control system and changing the resonance conditions of the magnetic field control system so as to compensate for the magnetic field difference between the first and second positions based on the resonance signal. A nuclear magnetic resonance apparatus characterized by: