JPH0664130B2 - A nuclear magnetic resonance apparatus for measuring the time course of biological samples. - Google Patents

Description

TECHNICAL FIELD The present invention relates to a nuclear magnetic resonance apparatus, and particularly to a sample suitable for measuring a specific biological sample over a long period of time at a preset time and obtaining a change with time. The present invention relates to a nuclear magnetic resonance apparatus capable of performing measurement.

[Conventional technology]

In recent years, the nuclear magnetic resonance apparatus has made great progress in two fields, high-resolution NMR for analysis and NMR-CT for human tomographic observation. With the development of computer technology, large-capacity data processing can be obtained cheaply. In high-resolution NMR for analysis, it is strongly desired that many samples can be automatically measured and data can be output. Among them, the automatic sample exchanger in molecular structure analysis can be measured in a desired measurement mode, but NMR measurement has begun to attract attention for changes in substances over a long period of time, metabolism of organisms, and the like.

[Problems to be solved by the invention]

The automatic sample exchanger for NMR for analysis simply introduces the samples placed in the sample stand of the exchanger into the detection part of the NMR and measures them. Since spectra of many samples can be obtained without the operator having to operate each sample, the operation rate of the apparatus is also improved, which is extremely useful. However, in recent years, biological research has become popular, and if one tries to automatically measure the time-dependent change of biological samples, one sample occupies the device during that period, leading to a decrease in operating rate, which is a problem. Vessel sample stands are unsuitable for side-by-side storage of biological samples.

[Object of the Invention]

An object of the present invention is to provide a nuclear magnetic resonance apparatus capable of efficiently performing measurement of a sample, including measurement of changes over time in a biological sample over time.

[Means for solving problems]

The conventional automatic sample exchanger has no problem when the sample is dissolved in the NMR sample tube with a solvent and ordinary NMR measurement is performed by simply arranging the sample tubes side by side, but the temperature of each biological sample can be set to an optimum value. is necessary.

The data processing device has a long-term timer, and has a software function of collecting data at a predetermined time by interruption of the timer. The software has a software function to select data from other samples in a time series manner.

That is, the present invention is, in addition to the conventional nuclear magnetic resonance apparatus, a sample storage means for respectively holding a plurality of samples including biological samples under a predetermined temperature condition, and a designated sample from the sample storage means at a measurement position in a magnetic field. And a sample automatic exchange means for returning to the sample storage means after completion of the measurement are provided, and a command is given to the sample automatic exchange means by the data processing device to sequentially carry a plurality of samples to the measurement position and perform the measurement, The biological sample is carried to a measurement position by interrupting it at predetermined fixed time intervals, and the measurement is performed to collect the change over time of the resonance spectrum data of the biological sample and the measurement data including the relaxation time.

〔Example〕

 Examples of the present invention will be described below.

FIG. 1 shows an embodiment of the present invention.

In the figure, the magnet unit 1 of the nuclear magnetic resonance apparatus is composed of a magnet 2 that creates a uniform DC magnetic field and a detection coil 4 that excites resonance to detect a resonance signal. The measurement sample 3 is placed in the detection coil [4]. Is inserted. Frequency source 8 that oscillates the resonance frequency
The high frequency wave is pulsed by the gate 9 and power amplified by the amplifier 10 and applied to the detection coil to excite resonance in the sample 3.
The decay of the resonance signal is picked up by the detection coil 4, amplified by the receiver 11, detected by the phase detector 12, and A /
The D converter 13 takes in the data processing device 14 as a digital amount and stores it in the storage device 15 each time. Generally 1
Acquisition of data that decays in time for one resonance signal is
It takes 16 seconds to finish in a few seconds. When this is FFTed, 1
A resonance spectrum whose frequency is on the horizontal axis of 6 kilopoints is obtained and displayed on the output device 16, and provides a lot of valuable information that is indispensable for molecular structure analysis. On the other hand, the sample storage device 6 is controlled to have an optimum temperature at which a biological sample is stored, where many samples 7 are installed. The automatic sample exchanger 5 takes out the specified sample from the data processing device from the sample storage device 6, carries it into the detection coil 4 in the magnet unit 1, and picks out the sample 3 which has been measured until then. It also returns the sample storage 6 to a predetermined place.

When many samples are measured sequentially in Fig. 2, for example,
An example of the operation of automatically measuring the change over time of the sample A by interrupting the measurement of the sample A at constant time intervals when measuring A, B, C, ... L will be described. Time t ₁ , t ₂ , t generated by timer 17
Sample A is introduced every ₃ and t ₄ and measured to store data. The measurement of the samples B, C ... Is carried out in the time period of the measurement.

FIG. 3 shows an example in which a series of data of the sample A is selected by the data processing device 14 from among mixed measurement data of other samples and displayed on the output device 16. This makes it easier to see the changes over time.

Although a high resolution NMR spectrum for analysis was shown in this example, a biological sample is generally inhomogeneous, and it is also applied to NMR-CT data in which a tomographic image can be obtained by applying a gradient magnetic field.

As for NMR-CT data, as explained in many books, three gradient magnetic fields orthogonal to each other are sequentially switched and applied (see the timing chart in Fig. [5]). It is widely known to create an image by applying to. Focusing on the hydrogen nucleus of an organism, the relaxation time differs between normal tissue and cancerous tissue, and it appears in the tomographic image of the relaxation time. For example, when investigating the effect of an anticancer drug, cancer cells were transplanted into a culture, and the cancer tissue was taken out several days after the administration of the anticancer drug, and the effect of the anticancer drug was observed from the weight. In this example, the process of culturing cancer tissue is obtained by storing the NMR-CT image of cancer cells at regular intervals from the administration of the anticancer drug. Moreover, since the cancer tissue is removed from the culture by the conventional method,
Although it is not possible to examine the effect of the anti-cancer agent by continuously culturing, according to the present example, the culture is not destroyed, so that it can be continuously performed. The embodiment of the present invention shown in FIG. 4 is the same as the embodiment shown in FIG. 1, and is equipped with a gradient magnetic field coil 18, a gradient magnetic field pulse generator [19], and a current amplifier 20 in order to obtain NMR-CT of a heterogeneous sample. Has been done.

〔The invention's effect〕

As described above, according to the present invention, it is possible to efficiently perform measurement of a sample including measurement of change over time in a biological sample over time.

Further, according to the present invention, the process of slowly changing over several days to several tens of days can be efficiently measured by NMR, so that the effect is extremely large. There is no factor that damages the biological sample at each measurement, and since the same sample collects data from the middle to the end, highly accurate data can be obtained, and the conventional method of destroying the sample to obtain the data in the middle is the first. Therefore, it is necessary to prepare a large number of samples, and the effect of the present invention is extremely large in view of the large variation in data.

[Brief description of drawings]

FIG. 1 is a block diagram showing an embodiment of the present invention, FIG. 2 is a diagram for explaining the operation of the embodiment of the present invention, FIG. 3 is a diagram for explaining an example of spectrum output of the embodiment of the present invention, and FIG. FIG. 5 is a diagram showing another embodiment of the present invention, and FIG. 5 is a time chart of the implementation shown in FIG. DESCRIPTION OF SYMBOLS 1 ... Magnet part of nuclear magnetic resonance apparatus, 2 ... DC magnet, 3 ... Sample, 4 ... Detection coil, 5 ... Sample automatic exchanger, 6 ... Sample storage, 7 ... Sample, 8 ... Frequency source, 9 ... Gate, 10 ... Power amplifier, 11 ... Receiver, 12 ... Phase detector, 13 ... A / D converter, 14 ... Data processing device, 15 ... Storage device, 16 ... Output device, 17 ... Timer, 18 ... Gradient magnetic field coil, 19 ... Gradient magnetic field pulse generator, 20 ... Pulse current amplifier.

Claims (2)

[Claims] 1. A magnet for generating a predetermined magnetic field, a frequency source for generating a predetermined high frequency, and a high frequency acting on a sample placed at a measurement position in the magnetic field to excite nuclear magnetic resonance and A nuclear magnetic resonance apparatus including a detection coil for receiving a resonance signal generated by excitation, and a data processing apparatus for calculating the resonance signal detected to obtain measurement data of the sample, and a biological sample Sample storage means for holding a plurality of samples respectively under a predetermined temperature condition, and a sample specified by a command of the data processing device,
And a sample automatic exchange means for carrying the sample storage means to a measurement position in the magnetic field and returning it to the sample storage means after completion of measurement, wherein the data processing device gives a command to the sample automatic exchange means, The sample is sequentially carried to the measurement position to perform the measurement, and the biological sample is carried to the measurement position by interrupting at a predetermined constant time interval to perform the measurement, and resonance spectrum data of the biological sample. And a nuclear magnetic resonance apparatus for measuring the change over time of biological samples, which collects the change over time of measurement data including relaxation time. 2. The nuclear magnetic resonance apparatus according to claim 1, wherein the biological sample is a culture of cancer cells to which an anticancer drug has been administered, and the time course of the biological sample. Nuclear magnetic resonance instrument for measurement.