APPARATUS AND METHOD FOR INVESTIGATING A SAMPLE BY USING NUCLEAR MAGNETIC RESONANCE AND A MAGNETORESISTANCE SENSOR

Abstract

The present invention relates to an apparatus (100) and method for investigating a sample by using nuclear magnetic resonance, particularly zero- to ultra-low-field nuclear magnetic resonance, the apparatus (100) comprising: a magnetically shielded chamber (20) for magnetically shielding the sample from external static magnetic fields; magnetic field pulse generation means (30) arranged in the magnetically shielded chamber (20) and configured to manipulate nuclear spins present in the sample, thereby causing the sample to produce a magnetic signal; andat least one magnetoresistive sensor (40) comprising a ferromagnetic material, wherein the at least one magnetoresistive sensor (40) is arranged in the magnetically shielded chamber (20) and configured to detect the magnetic signal produced by the sample.

Claims

1. An apparatus for investigating a sample by using nuclear magnetic resonance including zero- to ultra-low-field nuclear magnetic resonance, the apparatus comprising: a magnetically shielded chamber for magnetically shielding the sample from external static magnetic fields; a magnetic field pulse generation means arranged in the magnetically shielded chamber and configured to manipulate nuclear spins present in the sample, thereby causing the sample to produce a magnetic signal; and at least one magnetoresistive sensor comprising a ferromagnetic material, wherein the at least one magnetoresistive sensor is arranged in the magnetically shielded chamber and configured to detect the magnetic signal produced by the sample.

2. The apparatus according to claim 1, comprising: a demagnetization means which are configured to demagnetize the at least one magnetoresistive sensor.

3. The apparatus according to claim 2, further comprising: a measurement sequencing unit for controlling the magnetic field pulse generation means and the demagnetization means, wherein the measurement sequencing unit is configured to carry out a measurement sequence including a demagnetization sequence for demagnetizing the at least one magnetoresistive sensor, wherein the demagnetization sequence comprises the generation and/or application of a decaying sinusoidal wave magnetic field.

4. The apparatus according to claim 1, further comprising: a sensor holder for holding the at least one magnetoresistive sensor, wherein the sensor holder is arranged in the magnetically shielded chamber and further serves as a support for the magnetic field pulse generation means.

5. The apparatus according to claim 1, further comprising: a spin hyperpolarization means for hyperpolarizing nuclear spins present in the sample.

6. The apparatus according to claim 5, wherein the spin hyperpolarization means are configured to carry out a parahydrogen induced polarization.

7. The apparatus according to claim 1, wherein the magnetically shielded chamber comprises a first magnetic shield and a second magnet shield, wherein the second magnetic shield comprises a ferrite layer which is arranged between the first magnetic shield and the magnetoresistive sensor.

8. The apparatus according to claim 1, further comprising: a shuttling tube for shuttling the sample into the magnetically shielded chamber, and a solenoid wrapped around the shuttling tube.

9. The apparatus according to claim 1, further comprising: a computer-based data acquisition system which is coupled to the at least one magnetoresistive sensor and configured to record a detection signal from the at least one magnetoresistive sensor.

10. A method for investigating a sample by using nuclear magnetic resonance including zero- to ultra-low-field nuclear magnetic resonance, the method comprising: magnetically shielding the sample from external static magnetic fields by placing the sample into a magnetically shielded chamber; manipulating nuclear spins that are present in the sample by using magnetic field pulse generation means arranged in the magnetically shielded chamber, thereby causing the sample to produce a magnetic signal; and detecting the magnetic signal produced by the sample by using at least one magnetoresistive sensor which is arranged in the magnetically shielded chamber and which comprises a ferromagnetic material.

11. The method according to claim 10, wherein before detecting the magnetic signal produced by the sample, the at least one magnetoresistive sensor is demagnetized.

12. The method according to claim 11, wherein the magnetoresistive sensor is demagnetized in that a decaying sinusoidal wave magnetic field is generated in the vicinity of the magnetoresistive sensor by using demagnetization.

13. The method according to claim 11, wherein nuclear spins present in the sample are hyperpolarized before manipulating the spins.

14. The method according to claim 13, wherein the hyperpolarization is carried out by using parahydrogen-induced polarization methods.

15. The method according to claim 13, wherein the hyperpolarization of the nuclear spins present in the sample is carried out in-situ inside the magnetically shielded chamber and/or in-situ inside the sample.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0056] The above and other objects, features and advantages of the present invention will become more apparent upon reading of the following description of preferred embodiments and accompanying drawings. Other features and advantages of the subject-matter described herein will be apparent from the description and the drawings and from the claims. It should be understood that even though embodiments are separately described, single features and functionalities thereof may be combined without prejudice to additional embodiments. The present disclosure is illustrated by way of example and not limited by the accompanying figures.

[0057] Preferred embodiments of the present invention are exemplarily described regarding the following figures:

[0058] FIG. 1 shows a schematic representation of an apparatus according to a preferred embodiment of the present invention;

[0059] FIG. 2 shows a schematic representation of an apparatus according to another preferred embodiment of the present invention.

DETAILED DESCRIPTION OF THE FIGURES

[0060] The following description relates to exemplary embodiments of the present invention. Other embodiments of the invention are possible within the scope of the invention as defined by the appended claims. Throughout the figures, same reference signs are used for the same or similar elements.

[0061] FIG. 1 shows a conceptional sketch of an apparatus 100 for investigating a sample (not explicitly shown in the figure) by using Zero- to Ultra-Low Field Nuclear Magnetic Resonance (ZULF NMR) according to an exemplified embodiment of the present invention.

[0062] The apparatus 100 comprises a magnetically shielded chamber 20 for magnetically shielding the sample from external static magnetic fields. The apparatus further comprises magnetic field pulse generation means 30 in form of Helmholtz coils which are arranged in the magnetically shielded chamber 20 such that a magnetic field and/or magnetic field pulses can be generated in three dimensions. The Helmholtz coils 30 are configured to manipulate nuclear spins present in the sample, thereby causing the sample to produce a magnetic signal. Moreover, the apparatus comprises a magnetoresistive sensor 40 including a ferromagnetic material. The magnetoresistive sensor 40 is arranged in the magnetically shielded chamber 20 and configured to detect the magnetic signal produced by the sample.

[0063] The Helmholtz coils 30 further serve as demagnetization means which are configured to demagnetize the at least one magnetoresistive sensor 40. By means of a measurement sequencing unit (not shown in FIG. 1) which controls the Helmholtz coils 30, a measurement sequence including a demagnetization or degaussing sequence for demagnetizing the magnetoresistive sensor 40 can be applied. This ensures that the sensor 40 is not magnetized during investigation of the sample. Accordingly, the measurements of the sample are not influenced by the ferromagnetic magnetoresistive sensor 40.

[0064] In order to provide a ZULF region within the magnetically shielded chamber 20, the magnetically shielded chamber 20 is constituted by a first magnetic shield 22, which comprises four layers of Mu-metal, and a second magnetic shield 24 which comprises a ferrite layer and which is arranged between the first magnetic shield 22 and the magnetoresistive sensor 40. The ferrite layer 24 particularly serves for reducing or avoiding Johnson noise.

[0065] The apparatus 100 further comprises a sensor holder 50 for holding the magnetoresistive sensor 40. The sensor holder 50 is arranged in the magnetically shielded chamber 20 and further serves as a support for the Helmholtz coils 30.

[0066] Moreover, the apparatus 100 comprises spin hyperpolarization means for hyperpolarizing nuclear spins present in the sample. In the example shown in FIG. 1, the spin hyperpolarization means comprise a strong pre-polarizing magnet 70. Before investigating the sample in the magnetically shielded chamber 20, the sample is placed in an external magnetic field (of about 2 tesla) provided by the pre-polarizing magnet. Subsequently, the polarized sample is shuttled into the ZULF region within the magnetically shielded chamber 20.

[0067] Moreover, the apparatus 100 comprises a shuttling tube 60 for shuttling the sample into the magnetically shielded chamber 20. A solenoid 65 is wrapped around the shuttling tube 60. By means of the solenoid 65 wrapped around the shuttling tube 60, a guiding magnetic field can be applied to shuttle the sample into the magnetically shielded chamber 20.

[0068] Thus, in other words, the ZULF NMR apparatus shown in FIG. 1 is based on a magnetoresistive sensor or magnetoresistive magnetometer 40 placed in a 3D printed holder 50. The printed holder 50 also serves as a support for the three orthogonal Helmholtz pulse coils 30. The magnetometer 40 and pulse coil assembly 30 are centered within a four-layer Mu-metal and one layer ferrite magnetic shield. The magnetoresistive magnetometer 40 is oriented such that the sensitive axis is parallel to a longitudinal axis of the magnetically shielded chamber 20 (z-axis in FIG. 1). The distance between the center of the sample and the center of the magnetometer cell is 9.5 mm. The analog outputs of the magnetoresistive magnetometer 40 can be read out, for example, by an analog input card at 5000 samples/s. The projection of the magnetic field along the z-axis can be recorded. Background magnetic fields can be controlled via a set of coils built into the magnetically shielded chamber 20. The currents in the Bx, By, and Bz coils can be provided by a DC current source. A Gradient Driver Module (measurement sequencing unit) can be used for the control of experimental timing (using TTL outputs) and magnetic field pulse generation (using the analog output of the gradient module). In principle, experimental control can be achieved using any system with digital timing and analog output capabilities.

[0069] FIG. 2 shows a conceptional sketch of an apparatus 100 for investigating a sample (not explicitly shown in the figure) by using Zero- to Ultra-Low Field Nuclear Magnetic Resonance (ZULF NMR) according to another exemplified embodiment of the present invention. In this embodiment, the apparatus 100 comprises parahydrogen hyperpolarization means 72 instead of a pre-polarizing magnet as used in the embodiment of FIG. 1. As illustrated in FIG. 2, the parahydrogen hyperpolarization means 72, i.e., hyperpolarization means being configured to carry out parahydrogen induced polarization, comprise an inlet 76 and an outlet 78 for parahydrogen gas. Further, the parahydrogen hyperpolarization means 72 may comprise a source of hydrogen gas in the para-form (not shown in FIG. 2). Except for the hyperpolarization means, the other components of the apparatus 100 are similar to the components already described in connection with FIG. 1. For example, a solenoid 65 is used to controllably reach zero-field conditions. After hydrogenation, the sample is measured within the magnetically shielded chamber 20 by using magnetic field pulse generation means 30 and at least one magnetoresistive sensor 40.

[0070] For example, a sample may be measured via the following procedure: [0071] Polarizing, particularly hyperpolarizing, the sample, for example by placing the sample in a pre-polarizing high magnetic field (e.g. placing the sample in a pre-polarizing magnetic field of about 1.8 T for about 20 s) and/or by using other hyperpolarization techniques as described above (preferably a parahydrogen hyperpolarization); [0072] Shuttling the sample into the magnetically shielded chamber 20 or magnetically shielded detection region; [0073] While shuttling the sample, applying a guiding magnetic field using the solenoid 65 wrapped around the shuttling tube 60, as well as the z-axis Helmholtz pulsing coil; [0074] After the sample arrives next to the magnetoresistive sensor 40, adiabatically turning off the solenoid current; [0075] Then, suddenly (e.g. within 10 ms) turning off the x-axis pulse-coil current, resulting in an initial state of nuclear spins; Then, applying a magnetic field pulse (e.g. with a duration of 50 ms) along the x-axis; [0076] Immediately following the pulse, measuring the magnetic signal produced by the sample along the z-axis via the magnetoresistive sensor 40 (e.g. by reading out the analog output of the sensor by using an analog input card).

[0077] Within the present invention, the inventors could for the first time realize ZULF-NMR spectroscopy with magnetoresistance (e.g. GMR) detection. In particular, the present invention provides a high bandwidth and can potentially achieve spatial imaging. Further, the present invention can for example be applied with a microfluidic setup. This is because the small intrinsic size of the magnetoresistive sensor particularly matches for this purpose. Moreover, instead of a conventional remote detection, an in-situ detection can be carried out with the present invention.

[0078] The present invention works with a broad range of samples including but not limited to the following examples: [0079] [.sup.13C]methanol, thermally polarized [0080] [.sup.13C]sodium formate diluted in D.sub.2O (JCH=195 Hz), thermally polarized [0081] [.sup.13C]formic acid (JCH=222 Hz), thermally polarized [0082] [1-.sup.13C]fumarate, hyperpolarized by PHIP

[0083] In particular, the present invention works with any samples that are suitable for ZULF NMR.

LIST OF REFERENCE NUMERALS

[0084] 20 magnetically shielded chamber [0085] 22 Mu-metal layer (first magnetic shield) [0086] 24 ferrite layer (second magnetic shield) [0087] 30 system of Helmholtz coils (magnetic field generation means) [0088] 40 magnetoresistive sensor [0089] 50 sensor holder [0090] 60 shuttling tube [0091] 65 solenoid [0092] 70 pre-polarizing magnet (hyperpolarization means) [0093] 72 parahydrogen hyperpolarization means (hyperpolarization means) [0094] 100 NMR apparatus