Systems and methods for producing hyperpolarized materials - Patents.com

Abstract

Systems and methods for containing parahydrogen are disclosed. In some of the systems and methods, a gas cylinder is configured to contain hydrogen gas therein. The hydrogen gas may include parahydrogen gas at a first concentration of at least 45% and a pressure of up to 40 bar. The parahydrogen gas may have a decay time constant of at least 30 days. The parahydrogen gas may be for use in a PHIP, PHIP-SAH, SABRE, or PHIPNOESYS NMR or MRI experiment. In some of the systems and methods, a cryogenic chamber is configured to contain liquid hydrogen therein. The liquid hydrogen may include liquid parahydrogen at a concentration of at least 50 mole percent. The liquid hydrogen may be boiled to produce hydrogen gas containing at least 50 mole percent parahydrogen gas. The parahydrogen gas may be for use in a PHIP, PHIP-SAH, SABRE, or PHIPNOESYS NMR or MRI experiment.

Description

[Technical field]

[0001] cross reference This application claims priority to U.S. Provisional Patent Application No. 63 / 364,268, entitled "Parahydrogen gas obtained from liquid hydrogen," filed May 6, 2022, which is incorporated by reference in its entirety for all purposes.

[0002] The disclosed embodiments relate generally to the production of hyperpolarized materials for use in Nuclear Magnetic Resonance (NMR), Magnetic Resonance Imaging (MRI), or similar applications. [Background technology]

[0003] Nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) are techniques with important applications in chemistry, biology, and medical imaging. Despite their success, magnetic resonance applications require minute nuclear polarization of the analyte (typically 10 -5 It is recognized that there can often be limitations due to the small nuclear polarization (on the order of 100 nm). This small nuclear polarization can result in limited sensitivity compared to other analytical techniques such as mass spectrometry.

[0004] Increasing the nuclear spin polarization beyond the thermal equilibrium value can improve magnetic resonance sensitivity. Nuclear spin polarization can be increased using known techniques such as parahydrogen induced polarization (PHIP), PHIP-sidearm hydrogenation (PHIP-SAH), and signal amplification by reversible exchange (SABRE). Using such techniques, the nuclear spin polarization of a material can be increased by more than 10,000 times. The enhanced nuclear spin polarization can result in a proportional increase in NMR / MRI signal. This enhanced polarization decays over time due to the relaxation time of the nuclear spins in the polarized molecules, but for many molecules, the relaxation time can be on the order of seconds to minutes, during which an increase in polarization can result in a dramatic increase in NMR / MRI signal sensitivity. By enabling such a dramatic increase in NMR / MRI signal sensitivity, the increase in nuclear spin polarization can enable new applications such as imaging of in vivo metabolism using metabolites with increased nuclear spin polarization in MRI scanners, accelerating NMR spectroscopy investigations and enabling visualization of previously invisible molecular dynamics and structures. Summary of the Invention

[0005] According to the present disclosure, hydrogen gas, including parahydrogen gas, may be contained in a gas cylinder at a relatively low pressure and optionally at a relatively low volume. The parahydrogen gas may then be used by an end user, such as a hospital or clinic, in a nuclear magnetic resonance (NMR) or magnetic resonance imaging (MRI) experiment. For example, the parahydrogen gas may be used by an end user in a parahydrogen induced polarization (PHIP), PHIP-sidearm hydrolysis (PHIP-SAH), signal amplification by reversible exchange (SABRE), or PHIP nuclear Overhauser effect system (PHIPNOESYS) experiment. The relatively low pressure may allow the parahydrogen gas to decay to orthohydrogen gas at a relatively low rate, allowing the gas cylinder to be shipped to the end user and sufficient time for the end user to use the parahydrogen gas in a PHIP, PHIP-SAH, SABRE, or PHIPNOESYS experiment. The combination of the relatively low pressure and optionally at a relatively low volume may mitigate safety concerns associated with the use of flammable gas at high pressure.

[0006] According to the present disclosure, liquid hydrogen containing a high percentage of liquid parahydrogen can be produced and contained in a cryogenic vessel. The liquid hydrogen can then be boiled to obtain hydrogen gas containing a high percentage of parahydrogen gas. The parahydrogen gas can then be used by end users, such as hospitals or clinics, in NMR or MRI experiments. In some cases, the liquid hydrogen can be stored at a central distribution facility, such as a dispensing station. The liquid hydrogen can be boiled and used to fill gas cylinders or other gas canisters with hydrogen containing a high percentage of parahydrogen gas. The parahydrogen gas can then be used by end users. For example, the parahydrogen gas can be used by end users in PHIP, PHIP-SAH, SABRE, or PHIPNOESYS experiments. Due to the very long life of liquid parahydrogen, using liquid hydrogen containing a high percentage of liquid parahydrogen may significantly extend the shelf life of the parahydrogen source and may significantly simplify supply chain logistics associated with distributing parahydrogen to end users.

[0007] Disclosed embodiments include a system for containing parahydrogen gas. The system may include a gas cylinder configured to contain hydrogen gas therein. The hydrogen gas may include parahydrogen gas at a first concentration of at least 45% and at a pressure of up to 20 bar. The parahydrogen gas may have a decay time constant of at least 30 days. The parahydrogen gas may be for use in PHIP, PHIP-SAH, SABRE, or PHIPNOESYS NMR or MRI experiments.

[0008] Disclosed embodiments include a method for containing parahydrogen gas. The method can include containing hydrogen gas in a gas cylinder. The hydrogen gas can include parahydrogen gas at a first concentration of at least 45% and at a pressure of up to 20 bar. The parahydrogen gas can have a decay time constant of at least 30 days. The parahydrogen gas can be for use in PHIP, PHIP-SAH, SABRE, or PHIPNOESYS NMR or MRI experiments.

[0009] Disclosed embodiments include a system for generating parahydrogen gas. The system may include a cryogenic vessel. The cryogenic vessel may be configured to contain liquid hydrogen therein. The system may include a chamber fluidly connected to a cryogenic chamber. The chamber may be configured to receive liquid hydrogen from the cryogenic vessel. The chamber may be configured to boil the received liquid hydrogen, thereby forming a first hydrogen gas comprising at least 50 mole percent (mol%) parahydrogen gas. The parahydrogen gas may be for use in a PHIP, PHIP-SAH, SABRE, or PHIPNOESYS NMR or MRI experiment.

[0010] Disclosed embodiments include a method for generating parahydrogen gas. The method may include receiving liquid hydrogen and boiling the liquid hydrogen, thereby forming a first hydrogen gas comprising at least 50 mole % parahydrogen gas. The parahydrogen gas may be for use in a PHIP, PHIP-SAH, SABRE, or PHIPNOESYS NMR or MRI experiment.

[0011] It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the disclosed embodiments, as claimed.

[0012] The accompanying drawings, which form a part of this specification, illustrate certain embodiments and, together with the description, serve to explain principles and features of the disclosed embodiments. [Brief description of the drawings]

[0013] [Figure 1] FIG. 1 illustrates a first exemplary system for providing parahydrogen gas for use in Parahydrogen Induced Polarization (PHIP), PHIP-Side Arm Hydrolysis (PHIP-SAH), Signal Amplification by Reversible Exchange (SABRE), or PHIP Nuclear Overhauser Effect System (PHIPNOESYS) applications, according to disclosed embodiments.

[0014] [Diagram 2] FIG. 2 illustrates an exemplary decay curve showing the relationship between parahydrogen storage life and hydrogen gas pressure for hydrogen gas containing an initial parahydrogen concentration of 95%, according to disclosed embodiments.

[0015] [Diagram 3] FIG. 3 shows exemplary decay curves illustrating parahydrogen storage life for various gas cylinder purge conditions, according to disclosed embodiments.

[0016] [Figure 4]FIG. 4 illustrates a first exemplary method for providing parahydrogen gas for use in a PHIP, PHIP-SAH, SABRE, or PHIPNOESYS application, according to disclosed embodiments.

[0017] [Figure 5A] FIG. 5A illustrates a second exemplary system for providing parahydrogen gas for use in PHIP, PHIP-SAH, SABRE, or PHIPNOESYS applications, according to disclosed embodiments.

[0018] [Figure 5B] FIG. 5B illustrates a third exemplary system for providing parahydrogen gas for use in PHIP, PHIP-SAH, SABRE, or PHIPNOESYS applications, according to disclosed embodiments.

[0019] [Figure 6A] FIG. 6A illustrates a second exemplary method for providing parahydrogen gas for use in a PHIP, PHIP-SAH, SABRE, or PHIPNOESYS application, according to disclosed embodiments.

[0020] [Figure 6B] FIG. 6B illustrates a third exemplary method for providing parahydrogen gas for use in a PHIP, PHIP-SAH, SABRE, or PHIPNOESYS application, according to disclosed embodiments.

[0021] [Figure 7] FIG. 7 shows an exemplary Raman spectrum of a hydrogen gas mixture containing over 90% para-hydrogen produced from liquid hydrogen according to disclosed embodiments. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0022] Exemplary embodiments will now be described in detail and discussed with reference to the accompanying drawings. In some instances, the same reference numbers are used throughout the drawings, and the following description refers to the same or similar parts. Unless otherwise defined, technical and / or scientific terms have the meanings commonly understood by those skilled in the art. The disclosed embodiments are described in sufficient detail to enable those skilled in the art to practice the disclosed embodiments. It will be understood that other embodiments may be utilized and changes may be made without departing from the scope of the disclosed embodiments. Accordingly, the materials, methods, and examples are illustrative only and are not intended to be necessarily limiting.

[0023] NMR and MRI can be used in a wide range of applications, including but not limited to, determining chemical structures in synthetic intermediates, determining atomic-level structure and dynamics in proteins and nucleic acids, minimally invasive imaging of biological tissues or organisms, and even metabolic analysis of biological tissues or organisms. However, NMR and MRI can be limited in sensitivity due to the small size of nuclear magnetic moments combined with the corresponding small polarization at thermal equilibrium. This limited sensitivity may prevent the use of NMR and MRI in some applications and can make other applications of NMR and MRI impractically time- or material-intensive.

[0024] NMR and MRI can be improved by using higher magnetic fields and optimized detection systems. However, an alternative approach is to increase NMR and MRI by increasing the nuclear spin polarization to a level significantly higher than thermal equilibrium. Such hyperpolarization techniques can often increase NMR and MRI sensitivity by a factor significantly greater than increasing the magnetic field or using optimized detection systems.

[0025] Nuclear spin polarization can be increased using a variety of techniques, including dynamic nuclear polarization (DNP), parahydrogen-induced polarization (PHIP), PHIP-sidearm hydrolysis (PHIP-SAH), signal amplification by reversible exchange (SABRE), PHIP nuclear Overhauser effect system (PHIPNOESYS) spin exchange optical pumping (SEOP), optically initialized electronic triplet states (also called photoexcited triplet states, PETS), and other suitable methods. Among these techniques, parahydrogen-based methods such as PHIP, PHIP-SAH, SABRE, and PHIPNOESYS are particularly promising because they can be performed at high throughput using relatively low-cost equipment.

[0026] For example, recent work in NMR and MRI has demonstrated that NMR and MRI signals associated with various biorelevant contrast agents can be enhanced by several orders of magnitude using PHIP or PHIP-SAH. Such dramatic signal enhancement allows for spectroscopic analysis of the biorelevant contrast agent as it is metabolized by various tissues at different locations within the body. Analysis of the metabolic information determined by such spectroscopic imaging can allow for non-invasive determination of the health of tissues within the body. For example, abnormal metabolism of the biorelevant contrast agent can indicate disease, such as cancer, at several locations within the body.

[0027] In PHIP and PHIP-SAH, a derivative (e.g., a precursor) of the molecule of interest is reacted with para-hydrogen to form a para-hydrogenated form of the derivative. Spin order is then transferred from the proton added via the para-hydrogenation reaction to a nucleus of interest (such as a carbon-13 nucleus) contained within the molecule of interest. In PHIP, the para-hydrogenated form of the derivative is chemically identical to the molecule of interest and is distinguished from the molecule of interest only by the spin order derived from the para-hydrogenation reaction. In PHIP-SAH, the para-hydrogenated form of the derivative is cleaved (e.g., hydrolyzed) to obtain a hyperpolarized molecule of interest. In SABRE, the molecule of interest itself forms a coordination complex with a polarization transfer catalyst and para-hydrogen. Spin order is then transferred from the para-hydrogen to the nucleus of interest within the molecule of interest via the coordination complex. The molecule of interest is then optionally purified and used in an NMR or MRI procedure. PHIPNOESYS utilizes PHIP or PHIP-SAH to generate hyperpolarized material (e.g., a source compound) and transfer polarization from the source compound to a material (e.g., a target compound, target molecule, or molecule of interest) used in NMR spectroscopy. The transfer of polarization from the source compound to the target compound proceeds via an intermolecular Nuclear Overhauser Effect (NOE). PHIPNOESYS has been shown to increase the signal of NMR spectroscopy by up to approximately 2,000-fold, allowing NMR spectroscopy to be applied at significantly reduced concentrations than would otherwise be achievable.

[0028] PHIP, PHIP-SAH, SABRE, and PHIPNOESYS each require a source of parahydrogen to serve as a source of spin order that allows for hyperpolarization of the nuclei of interest. High concentrations of parahydrogen are typically produced by cooling gaseous hydrogen (e.g., to temperatures of 77 Kelvin (K), 25 K, or lower) in the presence of a paramagnetic catalyst. At room temperature, gaseous hydrogen contains about 25% parahydrogen (useful for PHIP, PHIP-SAH, SABRE, and PHIPNOESYS) and about 75% orthohydrogen (not useful for PHIP, PHIP-SAH, SABRE, and PHIPNOESYS). At significantly lower temperatures, orthohydrogen is converted to parahydrogen, increasing the concentration of parahydrogen in the hydrogen gas (e.g., the concentration of parahydrogen is about 50% at 77 K and over 98% at 25 K). In the current study, the hydrogen gas is then warmed and either used immediately in the PHIP, PHIP-SAH, SABRE, or PHIPNOESYS experiments, or stored in high-pressure gas cylinders for later use in such experiments.

[0029] As PHIP, PHIP-SAH, SABRE, and PHIPNOESYS move to more routine use, such as clinical applications, end users, such as hospitals or clinics, need access to a reliable source of parahydrogen gas. However, such end users have difficulty purchasing and maintaining the equipment required to generate parahydrogen on-site due to safety concerns associated with cryogenic temperatures, high pressure, and the use of highly flammable gases such as hydrogen. High pressure and flammability concerns also apply to the idea of ​​shipping high pressure cylinders filled with parahydrogen gas to such end users. Moreover, parahydrogen is easily converted to orthohydrogen at high pressure, and end users need to use their parahydrogen supply quickly. Therefore, shipping high pressure cylinders filled with parahydrogen to end users is also not ideal. Thus, there is a need for new systems and methods that allow parahydrogen to be shipped to end users while mitigating safety and time concerns.

[0030] The disclosed embodiments include hydrogen gas, including parahydrogen, in a gas cylinder at a relatively low pressure and optionally a relatively low volume. The parahydrogen gas may then be used by an end user, such as a hospital or clinic, in an NMR or MRI experiment. For example, the parahydrogen gas may be used by an end user in a PHIP, PHIP-SAH, SABRE, or PHIPNOESYS experiment. The relatively low pressure may allow the parahydrogen gas to decay to orthohydrogen gas at a relatively low rate, allowing the gas cylinder to be shipped to the end user and sufficient time for the end user to use the parahydrogen gas in a PHIP, PHIP-SAH, SABRE, or PHIPNOESYS experiment. The combination of the relatively low pressure and optionally a relatively low volume may mitigate safety concerns associated with the use of flammable gases at high pressure. As described herein, the disclosed embodiments may be used to polarize molecules of interest.

[0031] The disclosed embodiments produce and contain liquid hydrogen containing a high percentage of liquid para-hydrogen in a cryogenic vessel. The liquid hydrogen can then be boiled to obtain hydrogen gas containing a high percentage of para-hydrogen gas. The para-hydrogen gas can then be used by end users, such as hospitals or clinics, in NMR or MRI experiments. In some cases, the liquid hydrogen can be stored at a central distribution facility, such as a dispensing station. In some embodiments, the liquid hydrogen can be stored at a mobile distribution facility, such as a car-based or truck-based distribution facility. The liquid hydrogen can be boiled and used to fill gas cylinders or other gas canisters with hydrogen containing a high percentage of para-hydrogen gas. The para-hydrogen gas can then be used by end users. For example, the para-hydrogen gas can be used by end users in PHIP, PHIP-SAH, SABRE, or PHIPNOESYS experiments. Due to the very long life of liquid para-hydrogen, using liquid hydrogen containing a high percentage of liquid para-hydrogen may significantly extend the shelf life of the para-hydrogen source and may significantly simplify supply chain logistics associated with distributing para-hydrogen to end users.

[0032] Hyperpolarization and Parahydrogen As used in this disclosure, "polarization" refers to an imbalance in electronic or nuclear spin orientation. In some embodiments, the polarization can be the normalized, approximate difference between the number of spins in a first direction minus the number of spins in the opposite direction. As a non-limiting example, 200,000 1 Assuming a nuclear spin of H, a polarization of 2% can correspond to 102,000 spins in a first direction and 98,000 spins in the opposite direction. In some embodiments, "hyperpolarization" can include the polarization of a species (e.g., nuclear, selective, or the like) that exceeds the typical polarization level of that species observed at thermal equilibrium upon exposure to a particular magnetic field. As a non-limiting example, 1 A sample in a magnetic field of 1 T at thermal equilibrium with a H nuclear spin polarization greater than 0.000341% is substantially higher (e.g., at least one order of magnitude higher) than the 0.000341% thermal equilibrium polarization. 1 As a further non-limiting example, the ion beam may be hyperpolarized to have a H nuclear spin polarization of greater than 0.000257%. 13 A sample in a magnetic field of 3 T at thermal equilibrium with a spin polarization of C can be hyperpolarized. 15 A sample in a magnetic field of 3 T at thermal equilibrium with a spin polarization of N can be hyperpolarized.

[0033] As used in this disclosure, "hyperpolarization" describes a state in which the absolute value of the difference between a population of spin states (e.g., nuclear spin states, proton spin states, etc.) in one state (e.g., spin up) and a population of spin states in another state (e.g., spin down) exceeds the absolute value of the corresponding difference at thermal equilibrium.

[0034] Parahydrogen may be used as a polarization source consistent with disclosed embodiments. Parahydrogen is a form of molecular hydrogen in which two proton spins are in a singlet state, as described herein. The disclosed embodiments are not limited to a particular method of generating parahydrogen. Parahydrogen may be formed in gaseous or liquid form. In some embodiments, parahydrogen is generated in gaseous form by flowing hydrogen gas at low temperature through a chamber with a catalyst (e.g., iron oxide or another suitable catalyst). The hydrogen gas may contain both parahydrogen and orthohydrogen. The low temperature may bring the hydrogen gas to thermodynamic equilibrium in the chamber, increasing the population of parahydrogen.

[0035] As used in this disclosure, the population difference between two spin states is the difference between the populations of the two spin states divided by the total population of the two spin states. The population difference can be expressed as a fractional population difference or a percentage population difference. In some embodiments, the fractional population difference is at least about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or more, up to about 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, or less, or within a range defined by any two of the foregoing values.

[0036] Hydrogen gas may exhibit population differences between proton spin states at thermal equilibrium that are significantly greater than the population differences between the proton spin states. Hydrogen gas containing a high concentration of parahydrogen may have a large population difference between either the singlet spin state or the triplet spin state. In the case of Iz1Iz2 order, for example, there is a large population difference between the spin state |↑>|↓> and the spin state |↑>|↑>. The population difference of the proton spin states may be at least about 0.1 (e.g., a 10% difference in spin states or 55% of the parahydrogen molecules in the sample are in the singlet state and 45% are in the triplet state), 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or more, up to about 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, or less, or within a range defined by any two of the foregoing values.

[0037] System for providing low pressure parahydrogen gas 1 illustrates a first exemplary system 100 for providing parahydrogen gas for use in PHIP, PHIP-SAH, SABRE, or PHIPNOESYS NMR or MRI applications, according to disclosed embodiments. In the illustrated example, system 100 includes a gas cylinder 110. In some embodiments, gas cylinder 110 is configured to contain hydrogen gas therein. In some embodiments, gas cylinder 110 contains hydrogen gas therein.

[0038] In some embodiments, the hydrogen gas comprises parahydrogen gas at a first concentration. In some embodiments, the first concentration is at least about 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, 99.5%, 99.9%, or more. In some embodiments, the first concentration is up to about 99.9%, 99.5%, 99%, 95%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, or less. In some embodiments, the first concentration is within a range defined by any two of the aforementioned values. For example, in some embodiments, the first concentration is about 45% to about 99.9%, about 45% to about 99.5%, about 45% to about 99%, about 45% to about 95%, about 45% to about 90%, about 50% to about 99.9%, about 50% to about 99.5%, about 50% to about 99%, about 50% to about 95%, about 50% to about 90%, etc. In some embodiments, the first concentration is measured as a percentage of hydrogen molecules in the para-hydrogen state. For example, a first concentration of 45% means that 45% of the hydrogen molecules are in the para-hydrogen state and 55% of the hydrogen molecules are in the ortho-hydrogen state. The first concentration can be measured volume-to-volume (v / v), weight-to-weight (w / w), molar percent (mol%), or on another basis.

[0039] In some embodiments, the hydrogen gas comprises a pressure of up to about 100 bar, 95 bar, 90 bar, 85 bar, 80 bar, 75 bar, 70 bar, 65 bar, 60 bar, 55 bar, 50 bar, 45 bar, 40 bar, 35 bar, 30 bar, 25 bar, 20 bar, 19 bar, 18 bar, 17 bar, 16 bar, 15 bar, 14 bar, 13 bar, 12 bar, 11 bar, 10 bar, 9 bar, 8 bar, 7 bar, 6 bar, 5 bar, 4 bar, 3 bar, 2 bar, 1 bar, or less. In some embodiments, the hydrogen gas comprises a pressure of at least about 1 bar, 2 bar, 3 bar, 4 bar, 5 bar, 6 bar, 7 bar, 8 bar, 9 bar, 10 bar, 11 bar, 12 bar, 13 bar, 14 bar, 15 bar, 16 bar, 17 bar, 18 bar, 19 bar, 20 bar, 25 bar, 30 bar, 35 bar, 40 bar, 45 bar, 50 bar, 55 bar, 60 bar, 65 bar, 70 bar, 75 bar, 80 bar, 85 bar, 90 bar, 95 bar, 100 bar, or more. In some embodiments, the hydrogen gas comprises a pressure within a range defined by any two of the foregoing values.For example, in some embodiments, the hydrogen gas may be at a pressure between about 1 bar and about 40 bar, between about 1 bar and about 35 bar, between about 1 bar and about 30 bar, between about 1 bar and about 30 bar, between about 1 bar and about 20 bar, between about 1 bar and about 15 bar, between about 1 bar and about 10 bar, between about 1 bar and about 5 bar, between about 1 bar and about 4 bar, between about 1 bar and about 3 bar, between about 1 bar and about 2 bar, between about 2 bar and about 40 bar, between about 2 bar and about 35 bar, between about 2 bar and about 30 bar, between about 2 bar and about 25 bar, between about 2 bar and about 20 bar, About 2 bar to about 15 bar, about 2 bar to about 10 bar, about 2 bar to about 5 bar, about 2 bar to about 4 bar, about 2 bar to about 3 bar, about 3 bar to about 40 bar, about 3 bar to about 35 bar, about 3 bar to about 30 bar, about 3 bar to about 25 bar, about 3 bar to about 20 bar, about 3 bar to about 15 bar, about 3 bar to about 10 bar, about 3 bar to about 5 bar, about 3 bar to about 4 bar, about 4 bar to about 40 bar, about 4 bar to about 35 bar, about 4 bar to about 30 bar, about 4 bar to about 20 bar, about 4 bar to about 20 bar, about 4 bar to about 15 bar, about 4 bar to about 10 bar, about 4 bar to about 5 bar, about 5 bar to about 40 bar, about 5 bar to about 35 bar, about 5 bar to about 30 bar, about 5 bar to about 25 bar, about 5 bar to about 20 bar, about 5 bar to about 15 bar, about 5 bar to about 10 bar, about 10 bar to about 40 bar, about 10 bar to about 35 bar, about 10 bar to about 30 bar, about 10 bar to about 25 bar, about 10 bar to about 20 bar, about 10 bar to about This pressure range includes pressures such as 15 bar, about 15 bar to about 40 bar, about 15 bar to about 35 bar, about 15 bar to about 30 bar, about 15 bar to about 25 bar, about 15 bar to about 20 bar, about 20 bar to about 40 bar, about 20 bar to about 35 bar, about 20 bar to about 30 bar, about 20 bar to about 25 bar, about 25 bar to about 40 bar, about 25 bar to about 35 bar, about 25 bar to about 30 bar, about 30 bar to about 40 bar, about 30 bar to about 35 bar, and about 35 bar to about 40 bar.

[0040] In some embodiments, the hydrogen gas has a volume of up to about 250 standard liters, 240 standard liters, 230 standard liters, 220 standard liters, 210 standard liters, 200 standard liters, 190 standard liters, 180 standard liters, 170 standard liters, 160 standard liters, 150 standard liters, 140 standard liters, 130 standard liters, 120 standard liters, 110 standard liters, 100 standard liters, 95 standard liters, 90 standard liters, 85 standard liters, 80 standard liters, 75 standard liters, 70 standard liters, 65 standard liters, 60 standard liters, 55 standard liters, 50 standard liters, 45 standard liters, 40 standard liters, 35 standard liters, 30 standard liters, 25 standard liters, 20 standard liters, 15 standard liters, 10 standard liters, 5 standard liters, 1 standard liter, or less. In some embodiments, the hydrogen gas has a volume of at least 1 stdL, 5 stdL, 10 stdL, 15 stdL, 20 stdL, 25 stdL, 30 stdL, 35 stdL, 40 stdL, 45 stdL, 50 stdL, 55 stdL, 60 stdL, 65 stdL, 70 stdL, 75 stdL, 80 stdL, 85 stdL, 90 stdL, 95 stdL, 100 stdL, 110 stdL, 120 stdL, 130 stdL, 140 stdL, 150 stdL, 160 stdL, 170 stdL, 180 stdL, 190 stdL, 200 stdL, 210 stdL, 220 stdL, 230 stdL, 240 stdL, 250 stdL, or more. In some embodiments, the hydrogen gas has a volume that is within a range defined by any two of the foregoing values.

[0041] In some embodiments, the parahydrogen gas has a decay time constant of at least about 30 days, 35 days, 40 days, 45 days, 50 days, 55 days, 60 days, 65 days, 70 days, 75 days, 80 days, 85 days, 90 days, 95 days, 100 days, 110 days, 120 days, 130 days, 140 days, 150 days, 160 days, 170 days, 180 days, 190 days, 200 days, 225 days, 250 days, 275 days, 300 days, 325 days, 350 days, 375 days, 400 days, 425 days, 450 days, 475 days, 500 days, 525 days, 550 days, 575 days, 600 days, or more. In some embodiments, the parahydrogen gas has a decay time constant of at most about 600 days, 575 days, 550 days, 525 days, 500 days, 475 days, 450 days, 425 days, 400 days, 375 days, 350 days, 325 days, 300 days, 275 days, 250 days, 225 days, 200 days, 190 days, 180 days, 170 days, 160 days, 150 days, 140 days, 130 days, 120 days, 110 days, 100 days, 95 days, 90 days, 85 days, 80 days, 75 days, 70 days, 65 days, 60 days, 55 days, 50 days, 45 days, 40 days, 35 days, 30 days, or less. In some embodiments, the parahydrogen gas has a decay time constant that is within a range defined by any two of the foregoing values. In some embodiments, the decay time constant represents the decay time constant for the conversion of para-hydrogen molecules to ortho-hydrogen molecules. In some embodiments, the decay time constant represents the decay time constant for the conversion of para-hydrogen molecules to ortho-hydrogen molecules, eq =(C(t=0)-C eq )exp(-t / τ), where C(t) is the parahydrogen concentration at time t, C(t=0) is the initial parahydrogen concentration (i.e., the parahydrogen concentration at time t=0), and C eq is the thermal equilibrium parahydrogen concentration (approximately 25% at room temperature).

[0042] FIG. 2 shows an exemplary decay curve illustrating the relationship between parahydrogen shelf life and hydrogen gas pressure for hydrogen gas containing an initial parahydrogen concentration of 95% according to the disclosed embodiments. Shelf life t shelf was arbitrarily defined as the amount of time required for the parahydrogen concentration to decrease from its initial concentration of 95% to its final concentration of 85%.

number

[0043] Returning to the discussion of Figure 1, in some embodiments, the gas cylinder 110 is purged by at least one purge operation prior to receiving hydrogen gas therein. In some embodiments, the at least one purge operation includes at least one evacuation operation. In some embodiments, the at least one evacuation operation is performed by evacuating the gas cylinder 110 with a vacuum pump, such as, for example, a rotary pump, a scroll pump, a cryopump, a turbomolecular pump, an ion pump, a getter pump, or the like.

[0044] In some embodiments, the at least one purging operation includes at least one heating operation. In some embodiments, the at least one heating operation includes heating the gas cylinder 110. In some embodiments, the gas cylinder 110 is heated to a temperature of at least about 30 degrees (°C), 40°C, 50°C, 60°C, 70°C, 80°C, 90°C, 100°C, or more, up to about 100°C, 90°C, 80°C, 70°C, 60°C, 50°C, 40°C, 30°C, or less, or within a range defined by any two of the aforementioned values. In some embodiments, the at least one heating operation is performed before, during, or after the at least one evacuation operation.

[0045] In some embodiments, the at least one purging operation includes at least one filling operation. In some embodiments, the at least one filling operation is performed by filling the gas cylinder 110 with at least one gas. In some embodiments, the at least one gas includes an inert gas, such as nitrogen or argon. In some embodiments, the at least one gas includes hydrogen. In some embodiments, the at least one gas includes hydrogen having an increased concentration of parahydrogen compared to the thermal equilibrium parahydrogen concentration. In some embodiments, the gas has a purity of at least about 95%, 99%, 99.9%, 99.95%, 99.99%, 99.995%, 99.999%, 99.9995%, 99.9999%, or more, up to about 99.9999%, 99.9995%, 99.999%, 99.995%, 99.9%, 99.5%, 99%, 95%, or less, or defined by any two of the foregoing values. In some embodiments, the at least one filling operation is performed before or after the at least one draining operation or the at least one heating operation. In some embodiments, the at least one filling operation is performed by venting the gas cylinder 110.

[0046] In some embodiments, the at least one purge operation reduces the concentration of impurities or contaminants in the gas cylinder 110 prior to filling the gas cylinder 110 with hydrogen gas containing para-hydrogen. In some embodiments, the at least one purge operation reduces the concentration of trace gases such as oxygen, nitrogen, carbon dioxide, water vapor, and the like.

[0047] In some embodiments, the gas cylinder 110 has been purged for at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more purge operations prior to containing hydrogen gas therein. In some embodiments, the gas cylinder 110 has been purged for up to about 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 purge operations prior to containing hydrogen gas therein. In some embodiments, the gas cylinder 110 has been purged for a number of purge operations within a range defined by any two of the aforementioned values ​​prior to containing hydrogen gas therein.

[0048] FIG. 3 shows exemplary decay curves illustrating parahydrogen storage life for various gas cylinder purge conditions, according to disclosed embodiments. Gas cylinders were evacuated using a vacuum pump, subjected to various cleaning conditions, and filled with hydrogen gas containing an initial parahydrogen concentration of 90%. The cleaning conditions were: (1) untreated (no heating or filling operation) ("Untreated" in FIG. 3), (2) 4 alternating cycles of evacuation operation (with turbomolecular pump) and filling operation ("Turbo pumped to 8e-5 atm 4x purge cycles" in FIG. 3), and (3) 11 or more alternating cycles of evacuation operation (with turbomolecular pump) and filling operation (">10 purge cycles" in FIG. 3). As shown in FIG. 3, the decay constants were: (1) 17.8±3 days, (2) 22.9±1.8 days, and (3) 35.5±0.4 days. Thus, purging a gas cylinder prior to filling with hydrogen gas can significantly improve the life of parahydrogen.

[0049] Returning to the discussion of FIG. 1, in some embodiments, the system 100 further comprises a para-hydrogen generator (not shown in FIG. 1). In some embodiments, the para-hydrogen generator is coupled to the gas cylinder 110 during filling of the gas cylinder 110 with hydrogen gas. In some embodiments, the para-hydrogen generator is configured to generate hydrogen gas, including para-hydrogen gas at any first concentration described herein. In some embodiments, the para-hydrogen generator comprises a para-hydrogen generator as described in WO2022 / 157534, which is incorporated herein by reference in its entirety for all purposes.

[0050] In some embodiments, the system 100 further comprises a first flow system 120. In some embodiments, the first flow system 120 is fluidly coupled to the gas cylinder 110. In some embodiments, the first flow system 120 is configured to receive parahydrogen gas from the gas cylinder 110. In some embodiments, the first flow system comprises one or more gas pressure regulators, gas flow tubes, gas flow pumps, and / or gas flow valves configured to determine a rate at which the parahydrogen gas flows from the gas cylinder 110 through the first flow system 120. In some embodiments, the first flow system 120 comprises at least one compressor. In some embodiments, the at least one compressor is configured to increase a pressure of the parahydrogen gas above the pressure of the parahydrogen gas as provided by the gas cylinder 110. In some embodiments, increasing the pressure of the parahydrogen gas after storage increases the efficiency with which the parahydrogen gas may be used in a PHIP, PHIP-SAH, SABRE, or PHIPNOESYS procedure.

[0051] In some embodiments, the system 100 further comprises a mixing chamber 130. In some embodiments, the mixing chamber 130 is fluidly coupled to the first flow system 120. In some embodiments, the first flow system 120 is configured to direct parahydrogen gas from the gas cylinder 110 to the mixing chamber 130. In some embodiments, the mixing chamber 130 is configured to contain a first solution therein.

[0052] In some embodiments, the first solution is configured to generate a molecule of interest for use in a PHIP or PHIP-SAH experiment. In such embodiments, the first solution includes a molecule of interest or a derivative (e.g., a precursor) of a molecule of interest. In some embodiments, the molecule of interest is for use in an NMR or MRI procedure. In some embodiments, the mixing chamber 130 is configured to mix parahydrogen gas with the molecule of interest or a derivative of the molecule of interest. In some embodiments, the molecule of interest includes any bio-relevant imaging agent described herein.

[0053] In some embodiments, the mixing chamber 130 is configured to mix parahydrogen gas into the first solution such that the parahydrogen gas mixes with the molecule of interest. In some embodiments, the first solution contains a polarization transfer catalyst such as [IrCl(COD)(IMes)], where COD is cis,cis-1,5-cyclododecadiene and IMes is 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidin. In some embodiments, the parahydrogen gas is mixed with the molecule of interest in the presence of the polarization transfer catalyst. In some embodiments, the mixture of parahydrogen gas and the molecule of interest in the presence of the polarization transfer catalyst transfers spin order from the parahydrogen gas to the molecule of interest via SABRE interactions.

[0054] In some embodiments, the derivative of the molecule of interest includes at least one double or triple bond. In some embodiments, the mixing chamber 130 is configured to mix the parahydrogen gas with the first solution such that the parahydrogen gas mixes with the derivative of the molecule of interest. In some embodiments, the first solution contains a hydrogenation catalyst. In some embodiments, the parahydrogen gas is mixed with the derivative of the molecule of interest in the presence of the hydrogenation catalyst. In some embodiments, the mixture of the parahydrogen gas and the derivative of the molecule of interest in the presence of the hydrogenation catalyst induces a parahydrogenation reaction between the parahydrogen gas and the derivative of the molecule of interest.

[0055] In some embodiments, the parahydrogenation reaction hydrogenates at least one double or triple bond to form a molecule of interest. In some embodiments, spin order from the parahydrogen gas is transferred to the molecule of interest via a PHIP interaction. Examples of PHIP interactions can be found, for example, in WO2022 / 157534 and WO2022 / 018514, each of which is incorporated herein by reference in its entirety for all purposes.

[0056] In some embodiments, the para-hydrogenation reaction hydrogenates at least one double or triple bond to form a para-hydrogenated derivative of the molecule of interest. In some embodiments, the para-hydrogenated derivative of the molecule of interest is mixed with a hydrolysis agent, such as sodium hydroxide (NaOH) or potassium hydroxide (KOH). In some embodiments, the hydrolysis agent hydrolyzes the para-hydrogenated derivative of the molecule of interest to form a hydrolyzed side arm and the molecule of interest via a PHIP-SAH interaction. Examples of PHIP-SAH interactions can be found, for example, in WO2022 / 157534, WO2022 / 018514, and WO2021 / 198776, each of which is incorporated by reference in its entirety for all purposes.

[0057] In some embodiments, the system 100 further comprises a second flow system 140. In some embodiments, the second flow system 140 is fluidly coupled to the mixing chamber 130. In the example shown, the second flow system 140 comprises one or more liquid flow conduits, liquid flow pumps, and / or liquid flow valves configured to determine the flow rate at which the first solution flows from the mixing chamber 130.

[0058] In some embodiments, the system 100 further comprises a hydrolysis chamber 150. In some embodiments, the second flow system 140 is configured to direct the first solution to the hydrolysis chamber 150. In some embodiments, the hydrolysis chamber 150 is configured to receive the first solution after the first solution flows through the second flow system 140 to the hydrolysis chamber 150. In some embodiments, the hydrolysis chamber 150 is configured to mix the first solution with a hydrolysis agent, thereby hydrolyzing a para-hydrogenated derivative of the molecule of interest.

[0059] 1 is shown utilizing the second flow system 140 to flow the first solution to the hydrolysis chamber 150, system 100 need not be configured in such a manner. For example, the second flow system 140 may be configured to direct the hydrolysis agent to the mixing chamber 130, and the hydrolysis chamber 150 may be omitted. In such a case, the hydrolysis agent flows to the mixing chamber 130, and hydrolysis of the para-hydrogenated derivative of the molecule of interest occurs within the mixing chamber 130.

[0060] In some embodiments, the system 100 further comprises a third flow system 160. In some embodiments, the third flow system 160 is fluidly coupled to the hydrolysis chamber 150. In the example shown, the second flow system 160 comprises one or more liquid flow conduits, liquid flow pumps, and / or liquid flow valves configured to determine the flow rate at which the first solution flows from the hydrolysis chamber 150.

[0061] In some embodiments, the system 100 further comprises a purification chamber 170. In some embodiments, the second flow system 160 is configured to direct the first solution to the hydrolysis chamber 170. In some embodiments, the purification chamber 170 is configured to receive the first solution after the first solution flows through the third flow system 160 to the purification chamber 170. In some embodiments, the purification chamber 170 is configured to mix the first solution with the second solution, thereby forming a third solution containing the molecule of interest. In some embodiments, the third solution comprises a reduced concentration of contaminants compared to the first solution.

[0062] In some embodiments, the purification chamber 170 is configured to perform a precipitation reaction on the first solution. In some embodiments, the precipitation reaction forms a precipitate of the molecule of interest. In some embodiments, the purification chamber 170 is configured to mix the precipitate with a second solution, thereby forming a third solution. Examples of precipitation reactions are described, for example, in WO2022 / 018514 and WO2022 / 269350, each of which is incorporated herein by reference in its entirety for all purposes.

[0063] Although the third flow system 160 is shown to be utilized to flow the first solution to the purification chamber 170 in FIG. 1, the system 100 need not be configured in this manner. For example, the third flow system 160 may be configured to direct the second solution to the hydrolysis chamber 150, and the purification chamber 170 may be omitted. In such a case, the second solution flows to the hydrolysis chamber 150, and purification of the molecule of interest occurs within the hydrolysis chamber 150. Alternatively, the third flow system 160 may be configured to direct the second solution to the mixing chamber 130, and both the hydrolysis chamber 150 and the purification chamber 170 may be omitted. In such a case, the second solution flows to the mixing chamber 130, and purification of the molecule of interest occurs within the mixing chamber 130.

[0064] In some embodiments, the system 100 is configured to implement the method 400 described herein with respect to FIG.

[0065] Method for Providing Low Pressure Parahydrogen Gas - Patent application 4 illustrates a first exemplary method 400 for providing parahydrogen gas for use in a PHIP, PHIP-SAH, SABRE, or PHIPNOESYS NMR or MRI application, according to disclosed embodiments. In some embodiments, method 400 is performed using system 100 described herein with respect to FIG.

[0066] At step 410, hydrogen gas is contained within a gas cylinder. In some embodiments, the hydrogen gas comprises parahydrogen at any first concentration described herein. In some embodiments, the hydrogen gas comprises any pressure described herein. In some embodiments, the parahydrogen gas has any decay time constant described herein. In some embodiments, the hydrogen gas has any volume described herein. In some embodiments, the parahydrogen gas is for use in a PHIP, PHIP-SAH, SABRE, or PHIPNOESYS NMR or MRI procedure as described herein. In some embodiments, the gas cylinder has been purged with any number of purge operations described herein prior to containing the hydrogen gas within the gas cylinder. In some embodiments, method 400 includes purging the gas cylinder with any number of purge operations described herein prior to containing the hydrogen gas within the gas cylinder.

[0067] At step 420, the parahydrogen gas is mixed with any first solution described herein. In some embodiments, the pressure of the parahydrogen gas is increased above the pressure of the parahydrogen gas as supplied by a gas cylinder prior to mixing the parahydrogen gas with the first solution.

[0068] In some embodiments, parahydrogen gas is mixed with any molecule of interest described herein in the presence of any polarization transfer catalyst described herein. In some embodiments, such mixing transfers spin order from the parahydrogen gas to the molecule of interest via SABRE interactions as described herein. In some embodiments, the molecule of interest includes any molecule of interest described herein.

[0069] In some embodiments, parahydrogen gas is mixed with any derivative of any molecule of interest described herein in the presence of any hydrogenation catalyst described herein. In some embodiments, such mixing induces a parahydrogenation reaction between the parahydrogen gas and the derivative of the molecule of interest. In some embodiments, the parahydrogenation reaction hydrogenates at least one double or triple bond of the derivative of the molecule of interest, thereby forming the molecule of interest and transferring spin order from the parahydrogen gas to the molecule of interest via a PHIP interaction as described herein.

[0070] In some embodiments, parahydrogen gas is mixed with a derivative of the molecule of interest in the presence of any of the hydrogenation catalysts described herein. In some embodiments, such mixing induces a parahydrogenation reaction between the parahydrogen gas and the derivative of the molecule of interest. In some embodiments, the parahydrogenation reaction hydrogenates at least one double or triple bond of the derivative of the molecule of interest to form a parahydrogenated derivative of the molecule of interest. In some embodiments, the first solution containing the parahydrogenated derivative of the molecule of interest is mixed with any of the hydrolysis agents described herein. In some embodiments, the hydrolysis agent hydrolyzes the parahydrogenated derivative of the biomolecule of interest, thereby forming a hydrolyzed side arm and the molecule of interest via a PHIP-SAH interaction as described herein.

[0071] In some embodiments, the first solution is purified in step 430. In some embodiments, the first solution is purified using any purification method described herein. For example, in some embodiments, purifying the first solution includes mixing the first solution with a second solution, as described herein, thereby forming a third solution containing the molecule of interest. In some embodiments, the third solution includes a reduced concentration of contaminants compared to the first solution, as described herein. In some embodiments, purifying the first solution includes performing a precipitation reaction on the first solution, as described herein, thereby forming a precipitate of the molecule of interest, and mixing the precipitate of the molecule of interest with a second solution, as described herein, thereby forming a third solution containing the molecule of interest.

[0072] System for producing parahydrogen gas from liquid parahydrogen 5A illustrates a second exemplary system 500A for providing parahydrogen gas for use in a PHIP, PHIP-SAH, SABRE, or PHIPNOESYS application, according to disclosed embodiments. In the illustrated example, the system 500A includes a cryogenic vessel 510. In some embodiments, the cryogenic vessel 510 is configured to contain liquid hydrogen therein. In some embodiments, the cryogenic vessel 510 contains liquid hydrogen therein. In some embodiments, the liquid hydrogen comprises at least about 50 mol%, 55 mol%, 60 mol%, 65 mol%, 70 mol%, 75 mol%, 80 mol%, 85 mol%, 90 mol%, 95 mol%, or more liquid parahydrogen. In some embodiments, the liquid hydrogen comprises up to about 95 mol%, 90 mol%, 85 mol%, 80 mol%, 75 mol%, 70 mol%, 65 mol%, 60 mol%, 55 mol%, 50 mol%, or less liquid parahydrogen. In some embodiments, the liquid hydrogen comprises an amount of liquid parahydrogen within a range defined by any two of the preceding values.

[0073] In some embodiments, the cryogenic vessel 510 comprises a volume of at least about 1 liter (L), 2 L, 3 L, 4 L, 5 L, 6 L, 7 L, 8 L, 9 L, 10 L, 20 L, 30 L, 40 L, 50 L, 60 L, 70 L, 80 L, 90 L, 100 L, 200 L, 300 L, 400 L, 500 L, 600 L, 700 L, 800 L, 900 L, 1,000 L, or more. In some embodiments, the cryogenic vessel 510 comprises a volume of up to about 1,000 L, 900 L, 800 L, 700 L, 600 L, 500 L, 400 L, 300 L, 200 L, 100 L, 90 L, 80 L, 70 L, 60 L, 50 L, 40 L, 30 L, 20 L, 10 L, 9 L, 8 L, 7 L, 6 L, 5 L, 4 L, 3 L, 2 L, 1 L, or less. In some embodiments, the cryogenic vessel 510 comprises a volume within a range defined by any two of the foregoing values.

[0074] In some embodiments, the cryogenic vessel 510 includes a first vessel and a second vessel. In some embodiments, the first vessel is configured to contain liquid hydrogen therein. In some embodiments, the first vessel is located within the second vessel. In some embodiments, the second vessel is configured to reduce heat transfer from the ambient environment to the first vessel and the liquid hydrogen contained therein. In some embodiments, the second vessel is configured to be evacuated (i.e., subjected to low, medium, high, or ultra-high vacuum conditions) or is evacuated. In some embodiments, evacuating the second vessel reduces convective and conductive heat transfer from the ambient environment to the first vessel and the liquid hydrogen contained therein. In some embodiments, the second vessel is not configured to be evacuated or is not evacuated. In some embodiments, the cryogenic vessel 510 includes one or more radiation shields located between the first vessel and the second vessel. In some embodiments, the one or more radiation shields reduce radiative heat transfer from the ambient environment to the first vessel and the liquid hydrogen contained therein.

[0075] In some embodiments, the cryogenic vessel 510 comprises a first vessel, a second vessel, and a third vessel. In some embodiments, the first vessel is configured to contain liquid hydrogen therein. In some embodiments, the first vessel is located within the second vessel. In some embodiments, the second vessel is located within the third vessel. In some embodiments, the second vessel and the third vessel are configured to reduce heat transfer from the ambient environment to the first vessel and the liquid hydrogen contained therein. In some embodiments, the second vessel is configured to be evacuated (i.e., subjected to low, medium, high, or ultra-high vacuum conditions) or is evacuated. In some embodiments, evacuating the second vessel reduces convective and conductive heat transfer from the ambient environment to the first vessel and the liquid hydrogen contained therein. In some embodiments, the second vessel is not configured to be evacuated or is not evacuated. In some embodiments, the cryogenic vessel 510 includes one or more radiation shields located between the first vessel and the second vessel. In some embodiments, the one or more radiation shields reduce radiative heat transfer from the ambient environment to the first vessel and the liquid hydrogen contained therein. In some embodiments, the third vessel is configured to contain a cryogenic liquid therein (e.g., liquid nitrogen). In some embodiments, containing the cryogenic liquid in the third vessel reduces heat transfer from the ambient environment to the first vessel and the liquid hydrogen contained therein. In some embodiments, the cryogenic vessel 510 includes one or more radiation shields positioned between the first vessel and the third vessel. In some embodiments, the one or more radiation shields reduce radiative heat transfer from the ambient environment to the first vessel and the liquid hydrogen contained therein.

[0076] In some embodiments, the cryogenic vessel 510 comprises a first vessel, a second vessel, a third vessel, and a fourth vessel. In some embodiments, the first vessel is configured to contain liquid hydrogen therein. In some embodiments, the first vessel is located within the second vessel. In some embodiments, the second vessel is located within the third vessel. In some embodiments, the third vessel is located within the fourth vessel. In some embodiments, the second vessel, the third vessel, and the fourth vessel are configured to reduce heat transfer from the ambient environment to the first vessel and the liquid hydrogen contained therein. In some embodiments, the second vessel is configured to be evacuated (i.e., subjected to low, medium, high, or ultra-high vacuum conditions) or is evacuated. In some embodiments, evacuating the second vessel reduces convective and conductive heat transfer from the ambient environment to the first vessel and the liquid hydrogen contained therein. In some embodiments, the second vessel is not configured to be evacuated or is not evacuated. In some embodiments, the cryogenic vessel 510 includes one or more radiation shields located between the first vessel and the second vessel. In some embodiments, the one or more radiation shields reduce radiative heat transfer from the ambient environment to the first vessel and the liquid hydrogen contained therein. In some embodiments, the third vessel is configured to contain a cryogenic liquid therein (e.g., liquid nitrogen). In some embodiments, containing a cryogenic liquid in the third vessel reduces heat transfer from the ambient environment to the first vessel and the liquid hydrogen contained therein. In some embodiments, the cryogenic vessel 510 includes one or more radiation shields located between the first vessel and the third vessel. In some embodiments, the one or more radiation shields reduce radiative heat transfer from the ambient environment to the first vessel and the liquid hydrogen contained therein. In some embodiments, the fourth vessel is configured to be evacuated (i.e., subjected to low, medium, high, or ultra-high vacuum conditions) or is evacuated. In some embodiments, venting the fourth vessel reduces convective and conductive heat transfer from the ambient environment to the first vessel and the liquid hydrogen contained therein, hi some embodiments, the fourth vessel is not configured to be vented or is not vented.In some embodiments, the cryogenic vessel 510 includes one or more radiation shields located between the first vessel and the fourth vessel. In some embodiments, the one or more radiation shields reduce radiative heat transfer from the surrounding environment to the first vessel and the liquid hydrogen contained therein.

[0077] In some embodiments, system 500A comprises a chamber 520. In some embodiments, chamber 520 is fluidly coupled to cryogenic vessel 510. In some embodiments, chamber 520 is configured to receive liquid hydrogen from cryogenic vessel 510. In some embodiments, chamber 520 is configured to boil the received liquid hydrogen, thereby forming a first hydrogen gas. In some embodiments, chamber 520 comprises a heater configured to boil the received liquid hydrogen, thereby forming a first hydrogen gas. In some embodiments, the first hydrogen gas comprises at least about 50 mol%, 55 mol%, 60 mol%, 65 mol%, 70 mol%, 75 mol%, 80 mol%, 85 mol%, 90 mol%, 95 mol%, or more parahydrogen gas. In some embodiments, the first hydrogen gas comprises up to about 95 mol%, 90 mol%, 85 mol%, 80 mol%, 75 mol%, 70 mol%, 65 mol%, 60 mol%, 55 mol%, 50 mol%, or less of parahydrogen gas, hi some embodiments, the first hydrogen gas comprises an amount of parahydrogen gas within a range defined by any two of the foregoing values.

[0078] In some embodiments, system 500A includes a port 525. In some embodiments, port 525 is fluidly coupled to chamber 520. In some embodiments, port 525 is configured to fluidly couple chamber 520 to a gas cylinder or a fluid pump (not shown in FIG. 5A ). In some embodiments, the gas cylinder or fluid pump is configured to deliver a first hydrogen gas to the solution. In some embodiments, the solution includes a target molecule (also referred to herein as a target compound or a molecule of interest) or a precursor to the target molecule. In some embodiments, the target molecule or a precursor to the target molecule includes a molecule used in a PHIP, PHIP-SAH, SABRE, or PHIPNOESYS application. In some embodiments, the target molecule includes any biorelevant imaging agent described herein. In some embodiments, the solution further includes a catalyst, such as a hydrogenation catalyst.

[0079] In the example shown in FIG. 5A, system 500A is configured to generate a relatively high concentration of liquid para-hydrogen in liquid hydrogen. In some embodiments, system 500A is configured to generate a relatively high concentration of liquid para-hydrogen while hydrogen is in a liquid phase. For example, in some embodiments, cryogenic vessel 510 is configured to house a first para-hydrogen conversion catalyst therein. In some embodiments, the first para-hydrogen conversion catalyst is configured to convert liquid ortho-hydrogen contained in the liquid hydrogen to liquid para-hydrogen. In this manner, a relatively high concentration of liquid para-hydrogen may be generated directly in the liquid hydrogen.

[0080] 5B illustrates a third exemplary system 500B for providing parahydrogen gas for use in a PHIP, PHIP-SAH, SABRE, or PHIPNOESYS application, according to disclosed embodiments. In the illustrated example, system 500B includes a cryogenic vessel 510. In some embodiments, cryogenic vessel 510 includes any cryogenic vessel described herein with respect to FIG. 5A.

[0081] In some embodiments, the system 500B comprises a chamber 520. In some embodiments, the chamber 520 comprises any chamber described herein with respect to FIG.

[0082] In the example shown in FIG. 5B, system 500B is configured to first generate a relatively high concentration of gaseous para-hydrogen while the hydrogen is in the gas phase, and then generate a relatively high concentration of liquid para-hydrogen by condensing the gaseous hydrogen. For example, in some embodiments, system 500B optionally further comprises an airtight container 530. In some embodiments, airtight container 530 is configured to contain a second hydrogen gas therein. In some embodiments, airtight container 530 is configured to contain a second para-hydrogen conversion catalyst therein. In some embodiments, the second para-hydrogen conversion catalyst is configured to convert gaseous ortho-hydrogen in the second hydrogen gas to gaseous para-hydrogen. Thus, in some embodiments, the airtight vessel 530 is configured to produce a third hydrogen gas comprising a relatively large amount of gaseous parahydrogen therein (e.g., at least about 50 mol%, 55 mol%, 60 mol%, 65 mol%, 70 mol%, 75 mol%, 80 mol%, 85 mol%, 90 mol%, 95 mol% or more parahydrogen, up to about 95 mol%, 90 mol%, 85 mol%, 80 mol%, 75 mol%, 70 mol%, 65 mol%, 60 mol%, 55 mol%, 50 mol% or less parahydrogen, or an amount of parahydrogen that is within a range defined by any two of the foregoing values).

[0083] In some embodiments, system 500B optionally further comprises a condenser 540. In some embodiments, condenser 540 is fluidly coupled to airtight vessel 530. In some embodiments, condenser 540 is configured to receive the third hydrogen gas from airtight vessel 530, condense the third hydrogen gas, and generate liquid hydrogen from the third hydrogen gas. In some embodiments, condenser 540 is fluidly coupled to cryogenic vessel 510 and configured to deliver liquid hydrogen to cryogenic vessel 510.

[0084] In some embodiments, the first para-hydrogen conversion catalyst (described herein with respect to FIG. 5A) or the second para-hydrogen conversion catalyst (described herein with respect to FIG. 5B) comprises a material configured to (1) adsorb liquid or gaseous ortho-hydrogen, respectively, (2) split the liquid or gaseous ortho-hydrogen, respectively, and (3) release the liquid or gaseous ortho-hydrogen, respectively. In some embodiments, the first or second para-hydrogen conversion catalyst comprises a paramagnetic material. In some embodiments, the ortho-hydrogen comprises two hydrogen spins, and the first or second para-hydrogen conversion catalyst breaks the symmetry between the two hydrogen spins, thereby converting the ortho-hydrogen to para-hydrogen.

[0085] In some embodiments, the first or second parahydrogen conversion catalyst comprises gadolinium oxide, crude cerium oxide, neodymium oxide, FeCl2 on silica gel, paramagnetic Fe2O3 on porous glass, about 2% paramagnetic Fe2O3 on porous glass, paramagnetic Fe2O3 on Florex, about 15% paramagnetic Fe2O3 on Florex, ferric ammonium sulfate, magnetite, Fe3O4, Cr2O3 on alumina, paramagnetic Fe2O3 and Cr2O3 on alumina, about 15% paramagnetic Fe2O3 and about 9.3% Cr2O3 on alumina, Ni and thoria on alumina, about 5.3% Ni and about 0.24% thoria on alumina, MnO2 on silica gel, about 18% MnO2 on silica gel, Ni on alumina, about 0.5% Ni on alumina, hydrous manganese dioxide, hydrous ferric oxide, hydrated ferric oxide, or any possible combination of the foregoing materials.

[0086] Method for producing parahydrogen gas from liquid parahydrogen 6A illustrates a second exemplary method 600A for providing parahydrogen gas for use in a PHIP, PHIP-SAH, SABRE, or PHIPNOESYS NMR or MRI application, according to disclosed embodiments. In some embodiments, method 600A is performed using system 500A described herein with respect to FIG.

[0087] At step 610, liquid hydrogen is received. In some embodiments, the liquid hydrogen includes any of the liquid hydrogen described herein with respect to FIG. 5A. For example, in some embodiments, the liquid hydrogen includes at least about 50 mol%, 55 mol%, 60 mol%, 65 mol%, 70 mol%, 75 mol%, 80 mol%, 85 mol%, 90 mol%, 95 mol%, or more liquid parahydrogen. In some embodiments, the liquid hydrogen includes up to about 95 mol%, 90 mol%, 85 mol%, 80 mol%, 75 mol%, 70 mol%, 65 mol%, 60 mol%, 55 mol%, 50 mol%, or less liquid parahydrogen. In some embodiments, the liquid hydrogen includes an amount of liquid parahydrogen within a range defined by any two of the aforementioned values.

[0088] In some embodiments, the liquid hydrogen is received in any of the cryogenic vessels described herein with respect to Figure 5A. For example, in some embodiments, the liquid hydrogen is received in a volume of at least about 1 L, 2 L, 3 L, 4 L, 5 L, 6 L, 7 L, 8 L, 9 L, 10 L, 20 L, 30 L, 40 L, 50 L, 60 L, 70 L, 80 L, 90 L, 100 L, 200 L, 300 L, 400 L, 500 L, 600 L, 700 L, 800 L, 900 L, 1,000 L, or more, up to about 1,000 L, 90 L, 1,000 L, or more. The cryogenic vessel comprises a volume of 0L, 800L, 700L, 600L, 500L, 400L, 300L, 200L, 100L, 90L, 80L, 70L, 60L, 50L, 40L, 30L, 20L, 10L, 9L, 8L, 7L, 6L, 5L, 4L, 3L, 2L, 1L, or less, or a volume within a range defined by any two of the preceding values.

[0089] At step 620, the liquid hydrogen is boiled. In some embodiments, boiling the liquid hydrogen forms a first hydrogen gas. In some embodiments, the first hydrogen gas includes any first hydrogen gas described herein with respect to FIG. 5A. For example, in some embodiments, the first hydrogen gas includes at least about 50 molar%, 55 molar%, 60 molar%, 65 molar%, 70 molar%, 75 molar%, 80 molar%, 85 molar%, 90 molar%, 95 molar% or more parahydrogen gas, up to about 95 molar%, 90 molar%, 85 molar%, 80 molar%, 75 molar%, 70 molar%, 65 molar%, 60 molar%, 55 molar%, 50 molar% or less parahydrogen gas, or an amount of parahydrogen gas within a range defined by any two of the foregoing values.

[0090] In some embodiments, the method 600A further includes converting the liquid ortho-hydrogen to liquid para-hydrogen using a first para-hydrogen conversion catalyst. In some embodiments, the first para-hydrogen conversion catalyst includes any of the first para-hydrogen conversion catalysts described herein with respect to FIG. 5A.

[0091] In some embodiments, the method 600A further includes delivering a first hydrogen gas to the solution. In some embodiments, the solution includes any solution described herein with respect to FIG. 5A. In some embodiments, the solution includes any target molecule described herein with respect to FIG. 5A or any precursor to any target molecule. In some embodiments, the solution includes any catalyst described herein with respect to FIG. 5A. In some embodiments, the method 600A further includes hydrogenating the PHIP, PHIP-SAH, or PHIPNOESYS precursor using the first hydrogen gas to produce the target molecule. In some embodiments, the method 600A further includes delivering the target molecule to a subject or sample. In some embodiments, the method 600A further includes acquiring an NMR spectrum or an MRI image of the target sample in response to the target molecule.

[0092] 6B illustrates a third exemplary method 600B for providing parahydrogen gas for use in a PHIP, PHIP-SAH, SABRE, or PHIPNOESYS NMR or MRI application, according to disclosed embodiments. In some embodiments, method 600B is performed using system 500B described herein with respect to FIG.

[0093] A second hydrogen gas is obtained at step 602. In some embodiments, the second hydrogen gas includes any second hydrogen gas described herein with respect to FIG.

[0094] At step 604, the gaseous ortho-hydrogen in the second hydrogen gas is converted to gaseous para-hydrogen, thereby producing a third hydrogen gas. In some embodiments, the third hydrogen gas includes any third hydrogen gas described herein with respect to FIG. 5B. For example, in some embodiments, the third hydrogen gas includes at least about 50 mol%, 55 mol%, 60 mol%, 65 mol%, 70 mol%, 75 mol%, 80 mol%, 85 mol%, 90 mol%, 95 mol% or more gaseous para-hydrogen, up to about 95 mol%, 90 mol%, 85 mol%, 80 mol%, 75 mol%, 70 mol%, 65 mol%, 60 mol%, 55 mol%, 50 mol% or less gaseous para-hydrogen, or an amount of gaseous para-hydrogen within a range defined by any two of the foregoing values.

[0095] In some embodiments, the method 600B further includes converting the gaseous ortho-hydrogen to gaseous para-hydrogen using a second para-hydrogen conversion catalyst, hi some embodiments, the second para-hydrogen conversion catalyst includes any of the second para-hydrogen conversion catalysts described herein with respect to FIG.

[0096] In step 606, the third hydrogen gas is condensed, thereby producing liquid hydrogen.

[0097] At step 610, liquid hydrogen is received. In some embodiments, the liquid hydrogen includes any of the liquid hydrogen described herein with respect to FIG. 5B. For example, in some embodiments, the liquid hydrogen includes at least about 50 mol%, 55 mol%, 60 mol%, 65 mol%, 70 mol%, 75 mol%, 80 mol%, 85 mol%, 90 mol%, 95 mol%, or more liquid parahydrogen. In some embodiments, the liquid hydrogen includes up to about 95 mol%, 90 mol%, 85 mol%, 80 mol%, 75 mol%, 70 mol%, 65 mol%, 60 mol%, 55 mol%, 50 mol%, or less liquid parahydrogen. In some embodiments, the liquid hydrogen includes an amount of liquid parahydrogen within a range defined by any two of the aforementioned values.

[0098] In some embodiments, the liquid hydrogen is received in any of the cryogenic vessels described herein with respect to Figure 5B. For example, in some embodiments, the liquid hydrogen is received in a volume of at least about 1 L, 2 L, 3 L, 4 L, 5 L, 6 L, 7 L, 8 L, 9 L, 10 L, 20 L, 30 L, 40 L, 50 L, 60 L, 70 L, 80 L, 90 L, 100 L, 200 L, 300 L, 400 L, 500 L, 600 L, 700 L, 800 L, 900 L, 1,000 L, or more, up to about 1,000 L, 90 L, 1,000 L, or more. The cryogenic vessel comprises a volume of 0L, 800L, 700L, 600L, 500L, 400L, 300L, 200L, 100L, 90L, 80L, 70L, 60L, 50L, 40L, 30L, 20L, 10L, 9L, 8L, 7L, 6L, 5L, 4L, 3L, 2L, 1L, or less, or a volume within a range defined by any two of the preceding values.

[0099] At step 620, the liquid hydrogen is boiled. In some embodiments, boiling the liquid hydrogen forms a first hydrogen gas. In some embodiments, the first hydrogen gas includes any first hydrogen gas described herein with respect to FIG. 5B. For example, in some embodiments, the first hydrogen gas includes at least about 50 molar%, 55 molar%, 60 molar%, 65 molar%, 70 molar%, 75 molar%, 80 molar%, 85 molar%, 90 molar%, 95 molar% or more parahydrogen gas, up to about 95 molar%, 90 molar%, 85 molar%, 80 molar%, 75 molar%, 70 molar%, 65 molar%, 60 molar%, 55 molar%, 50 molar% or less parahydrogen gas, or an amount of parahydrogen gas within a range defined by any two of the foregoing values.

[0100] In some embodiments, the method 600B further includes delivering a first hydrogen gas to the solution. In some embodiments, the solution includes any solution described herein with respect to FIG. 5B. In some embodiments, the solution includes any target molecule described herein with respect to FIG. 5B or any precursor to any target molecule. In some embodiments, the solution includes any catalyst described herein with respect to FIG. 5B. In some embodiments, the method 600B further includes hydrogenating the PHIP, PHIP-SAH, or PHIPNOESYS precursor using the first hydrogen gas to produce the target molecule. In some embodiments, the method 600B further includes delivering the target molecule to a subject or sample. In some embodiments, the method 600B further includes obtaining an NMR spectrum or an MRI image of the target sample in response to the target molecule.

[0101] FIG. 7 shows an exemplary Raman spectrum of a hydrogen gas mixture containing over 90% para-hydrogen produced from liquid hydrogen according to disclosed embodiments. The liquid hydrogen was exposed to a para-hydrogen conversion catalyst to convert the liquid ortho-hydrogen to liquid para-hydrogen. The liquid hydrogen was boiled to form gaseous hydrogen. The gaseous hydrogen was analyzed using a homebuilt Raman spectrometer. The Raman spectrometer used a laser excitation of about 532 nanometers (nm) and 100 milliwatts (mW). The Raman peak corresponding to para-hydrogen occurred at about 542 nm. The Raman peaks corresponding to ortho-hydrogen occurred at about 549 nm and 556 nm. The areas under each peak were calculated to determine the concentrations of para-hydrogen and ortho-hydrogen in the hydrogen gas. To obtain the areas of the peaks, the peaks were fitted to Lorentzian functions. The anisotropy of the polarization tensor was taken into account during the calculation. Using this method, it was calculated that the hydrogen gas contained 95.2% para-hydrogen. Therefore, preparing para-hydrogen in a liquid state and boiling the liquid is a viable method for producing hydrogen gas containing high concentrations of para-hydrogen.

[0102] Bio-related contrast agents Disclosed embodiments include systems and methods for producing and utilizing biorelevant imaging agents with clinically relevant polarization, concentration, volume, or purity. In some embodiments, the method is for preparing an NMR material (also referred to herein as a "molecule of interest"). In some embodiments, the NMR material is suitable for use in NMR or MRI operations. In some embodiments, the NMR material increases the NMR or MRI signal and signal-to-noise ratio (SNR). In some embodiments, the NMR material is suitable for use in solution NMR spectroscopy. In some embodiments, the NMR material is a chemical compound. In some embodiments, the NMR material is a metabolite (e.g., a molecule with biorelevance, such as an amino acid, sugar, derivatives thereof), such as a metabolite suitable for use in NMR metabolomics applications. In some embodiments, the NMR material is suitable for in vitro probing of the metabolism of cell cultures or other biological tissues. In some embodiments, the NMR material is used in an NMR probe to investigate transient effects where high signal enhancement due to hyperpolarization is required, such as proton exchange between water and biomolecules. In some embodiments, the NMR material is a small molecule or metabolite suitable for injection into a cell, tissue, or organism for detection in an MRI scan. In some embodiments, the NMR material is introduced into a chamber for further analysis by NMR or MRI operation. In some embodiments, the NMR material is one or more deuterium ( 2 H) or carbon-13 ( 13 C) concentrated in atoms.

[0103] Consistent with the disclosed embodiments, the NMR material may include a bio-relevant contrast agent. In some embodiments, the bio-relevant contrast agent may be suitable for use in NMR or MRI operations. In some embodiments, the bio-relevant contrast agent may increase the NMR or MRI signal or signal-to-noise ratio (SNR). In some embodiments, the bio-relevant contrast agent may be suitable for use in solution NMR spectroscopy. In some embodiments, the bio-relevant contrast agent may be a metabolite (e.g., a molecule with bio-relevance, such as an amino acid, sugar, derivatives thereof, etc.), such as a metabolite suitable for use in NMR metabolomics applications. In some embodiments, the bio-relevant contrast agent is used for perfusion or contrast-enhanced imaging in MRI scans. In some embodiments, the bio-relevant contrast agent may be suitable for in vitro probing of the metabolism of cell cultures or other biological tissues. In some embodiments, the bio-relevant contrast agent is used for in vitro probing of the metabolism of cell cultures or other biological tissues. In some embodiments, the bio-relevant contrast agent may be used in NMR probes to investigate transient effects where high signal enhancement due to hyperpolarization is required, such as proton exchange between water and biomolecules. In some embodiments, the biorelevant imaging agent may be a small molecule or metabolite suitable for injection into a cell, tissue, or organism for detection in an MRI scan. In some embodiments, the biorelevant imaging agent may be introduced into the chamber for further analysis by NMR or MRI operation. In some embodiments, the biorelevant imaging agent may be one or more 2 H or 13 It is enriched in C atoms.

[0104] In some embodiments, the biorelevant imaging agent is pyruvate, lactate, alpha-ketoglutarate, bicarbonate, fumarate, urea, dehydroascorbate, glutamic acid, glutamine, acetate, dihydroxyacetone, acetoacetate, glucose, ascorbate, zymonate, alanine, fructose, imidazole, nicotinamide, nitroimidazole, pyrazinamide, isoniazid, conjugate acids of any of the above, natural and unnatural amino acids, esters thereof, or any of the foregoing. 2 H, 13C, or nitrogen-15 ( 15 N)-enriched versions. In some embodiments, the biologically relevant imaging agent includes pyruvate, lactate, alpha-ketoglutarate. In some embodiments, the biologically relevant imaging agent includes pyruvate. In some embodiments, the biologically relevant imaging agent includes lactate. In some embodiments, the biologically relevant imaging agent includes alpha-ketoglutarate (e.g., ethyl alpha-ketoglutarate).

[0105] In some embodiments, the biologically relevant imaging agent comprises at least one non-hydrogen nuclear spin. In some embodiments, the non-hydrogen nucleus comprises at least one spin 1 / 2 atom. In some embodiments, the non-hydrogen nuclear spin is 13 C or 15 N. In some embodiments, the biologically relevant imaging agent is at least partially isotopically labeled with non-hydrogen nuclear spins. In some embodiments, the biologically relevant imaging agent is at least partially enriched in non-hydrogen nuclear spins compared to an analog of the biologically relevant imaging agent that characterizes the non-hydrogen nuclear spins at their natural abundance. In some embodiments, the biologically relevant imaging agent is at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more, up to about 99%, 98%, 97%, 96%, The enrichment may be such that the non-hydrogen nuclear spins are characterized by an abundance of 95%, 94%, 93%, 92%, 91%, 90%, 85%, 80%, 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less, or an abundance within a range defined by any two of the foregoing values.

[0106] In some embodiments, the non-hydrogen nuclear spins are NMR inactive (i.e., spin 0) nuclei of an analog of a biologically relevant imaging agent that characterizes the non-hydrogen nuclear spins at their natural abundance (e.g., 12C or quadrupolar (i.e., spin >1 / 2) nuclei (e.g., nitrogen-14, 14 N) at their natural abundance. 13 The analogue of pyruvate that characterizes C is either C* of the structure H3C-C*(=O)-C*OOH, approximately 98.9% 12 C and about 1.1% 13 As a biorelevant imaging agent, pyruvate may contain one or both C* at any abundance as described herein. 13 To include C, instead 13 As used herein, *C and C* refer to 12 C or 13 As another example, carbon can be any of the C carbon isotopes at its natural abundance: 15 The analogue of urea that features N is approximately 99.6% N* in either of the structures H2N*-C(=O)-*NH2. 14 N and about 0.4% 15 As a biorelevant imaging agent, urea may contain one or both N* in any abundance as described herein. 15 To include N, instead 15 As used herein, *N and N* refer to 14 N or 15 Describes nitrogen, which can be any of the nitrogen isotopes of N.

[0107] Transport of liquid and / or gaseous parahydrogen Parahydrogen may be generated at a first location (e.g., in a gas cylinder described herein or in a cryogenic vessel described herein) and then transported to a second location for use. In some embodiments, the first location is a physical location such as a room, a laboratory, a specific warehouse, a hospital, an automobile, a truck, or other location where parahydrogen is generated. In some embodiments, the gas cylinder or cryogenic vessel is cooled to a temperature below room temperature before, during, or after transport. For example, in some embodiments, the gas cylinder or cryogenic vessel is cooled to a temperature below about 200K, 190K, 180K, 170K, 160K, 150K, 140K, 130K, 120K, 110K, 100K, 90K, 80K, 70K, 60K, 50K, or lower, above about 50K, 60K, 70K, 80K, 90K, 100K, 110K, 120K, 130K, 140K, 150K, 160K, 170K, 180K, 190K, 200K, or higher, or within a range defined by any two of the foregoing values. In some embodiments, the gas cylinder or cryogenic vessel is cooled using ice, dry ice, or liquid nitrogen. In some embodiments, cooling the gas cylinder or cryogenic vessel extends the life of the gaseous or liquid parahydrogen contained therein.

[0108] The generated parahydrogen may be transported in a gas cylinder or cryogenic container to a second location. The second location may be different from the first location. The gas cylinder or cryogenic container may be transported by vehicle or person. Transporting the parahydrogen may involve moving the gas cylinder or cryogenic container within the same location, such as from one part of a room to another part of a room. Transporting the gas cylinder or cryogenic container may involve moving the gas cylinder or cryogenic container from one room in a building to a different room in the same building or to a nearby building. Transporting the gas cylinder or cryogenic container may involve moving the gas cylinder or cryogenic container to a different location in the same city, a different city, a different state, a different province, a different region, a different country, or even a different continent. Transporting the gas cylinder or cryogenic container may involve bringing the gas cylinder or cryogenic container into the vicinity of an NMR or MRI device. Transporting the gas cylinder or cryogenic container may involve packaging or shipping the gas cylinder or cryogenic container in a suitable container.

[0109] Precipitation In various embodiments, the molecule of interest may be crystallized or precipitated from the solution described herein. The disclosed embodiments are not limited to any particular method of inducing such precipitation. For example, such precipitation may be induced via a change in temperature or pH, application of an electromagnetic stimulus (e.g., optical radiation such as ultraviolet radiation or optical radiation at another suitable wavelength or wavelengths), a mechanical stimulus (e.g., ultrasound, agitation, or another suitable mechanical stimulus), addition of another solute or solvent to the solution, or another suitable method, or any combination thereof. In some embodiments, after precipitation, the molecule of interest may be separated from the solution (e.g., using a filter, or another suitable method). In some embodiments, the molecule of interest may then be combined with another solution or redissolved. This solution may have desirable properties (e.g., biocompatibility, concentration, volume, temperature, pH, polarity, or other relevant properties, or any combination thereof) for the intended NMR or MRI application.

[0110] Use of molecules of interest In some embodiments, at least a portion of the molecule of interest may be injected into a subject or patient for use in an MRI experiment. In various embodiments, at least a portion of the molecule of interest may be used in NMR spectroscopy. At least one NMR or MRI pulse sequence may be applied to the molecule of interest.

[0111] The foregoing description has been presented for purposes of illustration, and is not exhaustive or limited to the precise forms or embodiments disclosed. Modifications and adaptations of the embodiments will be apparent from consideration of the specification and practice of the disclosed embodiments. For example, while the described implementations include hardware, systems and methods consistent with the present disclosure can be implemented using both hardware and software. Further, while certain components are described as being coupled together, such components may be integrated with each other or distributed in any suitable manner.

[0112] Furthermore, although exemplary embodiments are described herein, the scope includes any and all embodiments having equivalent elements, modifications, omissions, combinations (e.g., aspects across various embodiments), adaptations, or modifications based on the present disclosure. The elements of the claims should be interpreted broadly based on the language used in the claims, and not limited to the examples described herein or during the prosecution of the application, which examples should be interpreted as non-exclusive. Furthermore, the steps of the methods of the present disclosure can be modified in any manner, including rearranging steps, or inserting or deleting steps.

[0113] The features and advantages of the present disclosure are apparent from the detailed specification, and therefore, the appended claims are intended to cover all systems and methods that fall within the true spirit and scope of the present disclosure. As used herein, the indefinite articles "a" and "an" mean "one or more." Similarly, the use of a plural word does not necessarily imply a plurality, unless ambiguous in a given context. Furthermore, since numerous modifications and variations will readily occur from the study of this disclosure, it is not desired to limit the disclosure to the exact construction and operation illustrated and described. Accordingly, all suitable modifications and equivalents may be utilized to fall within the scope of the present disclosure.

[0114] As used herein, unless specifically stated otherwise, the term "or" includes all possible combinations, including both conjunctions and disjunctions, unless impracticable. For example, if a component is described as including A or B, the component may include only A, or only B, or A and B, unless specifically stated otherwise or impracticable. As a second example, if a component is described as including A, B, or C, the component may include only A, or only B, or only C, or A and B, or A and C, or B and C, or A and B and C.

[0115] Enumeration of embodiments Embodiment 1. A system comprising: a gas cylinder configured to contain hydrogen gas therein, the hydrogen gas comprising parahydrogen gas at a first concentration of at least 45% and at a pressure of up to 40 bar; the parahydrogen gas has a decay time constant of at least 30 days; The system, wherein the parahydrogen gas is for use in a parahydrogen induced polarization (PHIP), PHIP-side arm hydrolysis (PHIP-SAH), signal amplification by reversible exchange (SABRE), or PHIP nuclear Overhauser effect system (PHIPNOESYS), nuclear magnetic resonance (NMR) or magnetic resonance imaging (MRI) procedure.

[0116] Embodiment 2. The system of embodiment 1, wherein the first concentration is at least 95%.

[0117] Embodiment 3. A system as described in embodiment 1 or 2, wherein the pressure is up to 12 bar and the decay time constant is at least 30 days.

[0118] Embodiment 4. A system according to any one of embodiments 1 to 3, wherein the pressure is up to 3 bar and the decay time constant is at least 100 days.

[0119] Embodiment 5. The system of any one of embodiments 1-4, wherein the gas cylinder has been purged with at least one purge operation to contain hydrogen gas therein.

[0120] Embodiment 6. The system of embodiment 5, wherein the at least one purge operation includes at least one portion selected from the group consisting of at least one evacuation operation, at least one heating operation, and at least one filling operation.

[0121] Embodiment 7. A method for producing a gas-mixing system comprising the steps of: a first flow system configured to direct the parahydrogen gas to the mixing chamber; a mixing chamber configured to receive a first solution therein; a first solution containing a molecule of interest or a derivative of a molecule of interest; the molecule of interest is for use in an NMR or MRI procedure, 7. The system of any one of embodiments 1-6, wherein the mixing chamber is configured to mix parahydrogen gas with the molecule of interest or a derivative of the molecule of interest.

[0122] Embodiment 8. The system of embodiment 7, wherein the mixing chamber is configured to mix parahydrogen gas with the molecule of interest in the presence of a polarization transfer catalyst, thereby transferring spin order from the parahydrogen gas to the molecule of interest via a SABRE interaction.

[0123] Embodiment 9. The system of embodiment 7, wherein the derivative of the molecule of interest comprises at least one double or triple bond, and the mixing chamber is configured to mix parahydrogen gas with the derivative of the molecule of interest in the presence of a hydrogenation catalyst, thereby inducing a parahydrogenation reaction between the parahydrogen gas and the derivative of the molecule of interest, thereby hydrogenating the at least one double or triple bond and forming the molecule of interest, and transferring spin order from the parahydrogen gas to the molecule of interest via a PHIP interaction.

[0124] Embodiment 10. The system of embodiment 7, wherein the derivative of the molecule of interest comprises at least one double or triple bond, and the mixing chamber is configured to mix parahydrogen gas with the derivative of the molecule of interest in the presence of a hydrogenation catalyst, thereby inducing a parahydrogenation reaction between the parahydrogen gas and the derivative of the molecule of interest, thereby hydrogenating the at least one double or triple bond and forming a parahydrogenated derivative of the molecule of interest.

[0125] Embodiment 11. The method further comprises a second flow system fluidly connected to the mixing chamber and the hydrolysis chamber, a second flow system configured to direct a first solution containing the para-hydrogenated derivative of the molecule of interest to the hydrolysis chamber; a hydrolysis chamber configured to receive a first solution containing a para-hydrogenated derivative of a molecule of interest; 10. The system of embodiment 9, wherein the hydrolysis chamber is configured to mix a first solution containing the para-hydrogenated derivative of the molecule of interest with a hydrolysis agent, thereby hydrolyzing the para-hydrogenated derivative of the molecule of interest, thereby forming a hydrolyzed side arm and the molecule of interest via the PHIP-SAH interaction.

[0126] Embodiment 12. The method further comprises a third flow system fluidly connected to the mixing chamber or the hydrolysis chamber and the purification chamber, 12. The system of any one of embodiments 7 to 11, wherein a third flow system is configured to direct a first solution containing the molecule of interest to the purification chamber.

[0127] Embodiment 13. The system of embodiment 12, wherein the purification chamber is configured to mix a first solution containing the molecule of interest with a second solution, thereby forming a third solution containing the molecule of interest, the third solution comprising a reduced concentration of contaminants compared to the first solution.

[0128] Embodiment 14. The system of embodiment 13, wherein the purification chamber is configured to perform a precipitation reaction on a first solution containing the molecule of interest, thereby forming a precipitate of the molecule of interest, and to mix the precipitate of the molecule of interest with a second solution, thereby forming a third solution containing the molecule of interest, the third solution comprising a reduced concentration of contaminants compared to the first solution.

[0129] Embodiment 15. The system of any one of embodiments 7 to 14, wherein the molecule of interest comprises a biologically relevant imaging agent selected from the group consisting of pyruvate, glutamate, glutamine, lactate, acetate, acetoacetate, zymonate, alanine, fructose, fumarate, bicarbonate, urea, dehydroascorbate, alpha-ketoglutarate, dihydroxyacetone, glucose, ascorbate, and their conjugate acids.

[0130] Embodiment 16. A method comprising: storing hydrogen gas in a gas cylinder, the hydrogen gas comprising parahydrogen gas at a first concentration of at least 45% and at a pressure of up to 40 bar; the parahydrogen gas has a decay time constant of at least 30 days; The method, wherein the parahydrogen gas is for use in a parahydrogen induced polarization (PHIP), PHIP-sidearm hydrolysis (PHIP-SAH), signal amplification by reversible exchange (SABRE), or PHIP nuclear Overhauser effect system (PHIPNOESYS), nuclear magnetic resonance (NMR) or magnetic resonance imaging (MRI) procedure.

[0131] Embodiment 17. The method of embodiment 16, wherein the first concentration is at least 95%.

[0132] Embodiment 18. The method of embodiment 16 or 17, wherein the pressure is up to 12 bar and the decay time constant is at least 30 days.

[0133] Embodiment 19. The method of any one of embodiments 16 to 18, wherein the pressure is up to 3 bar and the decay time constant is at least 100 days.

[0134] Embodiment 20. The method of any one of embodiments 16-19, wherein the gas cylinder has been purged with at least one purge operation prior to containing hydrogen gas therein.

[0135] Embodiment 21. The method of embodiment 20, wherein the at least one purge operation includes at least one portion selected from the group consisting of at least one evacuation operation, at least one heating operation, and at least one filling operation.

[0136] Embodiment 22. The method further comprising mixing parahydrogen gas with the first solution; a first solution containing a molecule of interest or a derivative of a molecule of interest; The method of any one of embodiments 16-21, wherein the molecule of interest is for use in an NMR or MRI procedure.

[0137] Embodiment 23. The method of embodiment 22, further comprising mixing parahydrogen gas with the molecule of interest in the presence of a polarization transfer catalyst, thereby transferring spin order from the parahydrogen gas to the molecule of interest via a SABRE interaction.

[0138] Embodiment 24. The method of embodiment 22, further comprising mixing parahydrogen gas with a derivative of the molecule of interest in the presence of a hydrogenation catalyst, thereby inducing a parahydrogenation reaction between the parahydrogen gas and the derivative of the molecule of interest, thereby hydrogenating at least one double or triple bond of the derivative of the molecule of interest to form the molecule of interest, and transferring spin order from the parahydrogen gas to the molecule of interest via a PHIP interaction.

[0139] Embodiment 25. The method of embodiment 22, further comprising combining parahydrogen gas with a derivative of the molecule of interest in the presence of a hydrogenation catalyst, thereby inducing a parahydrogenation reaction between the parahydrogen gas and the derivative of the molecule of interest, thereby hydrogenating at least one double or triple bond of the derivative of the molecule of interest and forming a parahydrogenated derivative of the molecule of interest.

[0140] Embodiment 26. The method of embodiment 25, further comprising mixing the first solution containing the para-hydrogenated derivative of the molecule of interest with a hydrolysis agent, thereby hydrolyzing the para-hydrogenated derivative of the biomolecule of interest, thereby forming a hydrolyzed side arm and the molecule of interest via the PHIP-SAH interaction.

[0141] Embodiment 27. The method of any one of embodiments 22 to 26, further comprising purifying the first solution containing the molecule of interest.

[0142] Embodiment 28. The method of embodiment 27, wherein purifying the first solution containing the molecule of interest comprises mixing the first solution containing the molecule of interest with a second solution, thereby forming a third solution containing the molecule of interest, the third solution comprising a reduced concentration of the contaminant compared to the first solution.

[0143] Embodiment 29. The method of embodiment 27, wherein purifying the first solution containing the molecule of interest comprises performing a precipitation reaction on the first solution containing the molecule of interest, thereby forming a precipitate of the molecule of interest, and mixing the precipitate of the molecule of interest with a second solution, thereby forming a third solution containing the molecule of interest, wherein the third solution comprises a reduced concentration of contaminants compared to the first solution.

[0144] Embodiment 30. The method of any one of embodiments 22-29, wherein the molecule of interest comprises a biologically relevant imaging agent selected from the group consisting of pyruvate, glutamate, glutamine, lactate, acetate, acetoacetate, zymonate, alanine, fructose, fumarate, bicarbonate, urea, dehydroascorbate, alpha-ketoglutarate, dihydroxyacetone, glucose, ascorbate, and their conjugate acids.

[0145] Embodiment 31. A system comprising: a cryogenic vessel configured to contain liquid hydrogen therein; and a chamber fluidly connected to the cryogenic vessel, the chamber configured to receive liquid hydrogen from the cryogenic vessel and boil the received liquid hydrogen, thereby forming a first hydrogen gas comprising at least 50, 55, 60, 65, 70, 75, 80, 85, 90, or 95 mole percent parahydrogen gas.

[0146] Embodiment 32. The system described in embodiment 31, further comprising a port fluidly connected to the chamber, the port being configured to fluidly connect the chamber to a gas cylinder or a fluid pump.

[0147] Embodiment 33. The system of embodiment 32, wherein the gas cylinder or fluid pump is configured to deliver a first hydrogen gas to a solution containing a precursor to a target molecule and a catalyst, thereby hydrogenating the precursor in the presence of the catalyst and thereby forming the target molecule.

[0148] Embodiment 34. The system of embodiment 33, wherein the precursor comprises a parahydrogen induced polarization (PHIP) precursor or a PHIP side-arm hydrogenation (PHIP-SAH) precursor.

[0149] Embodiment 35. A system described in any one of embodiments 31 to 34, wherein the chamber comprises a heater configured to boil the received liquid hydrogen.

[0150] Embodiment 36. The system of any one of embodiments 31-35, wherein the liquid hydrogen comprises at least 50, 55, 60, 65, 70, 75, 80, 85, 90, or 95 mole percent liquid parahydrogen.

[0151] Embodiment 37. The system of any one of embodiments 31-36, wherein the cryogenic vessel is further configured to house a first para-hydrogen conversion catalyst therein, the first para-hydrogen conversion catalyst being configured to convert liquid ortho-hydrogen to liquid para-hydrogen.

[0152] 38. an airtight vessel configured to contain a second hydrogen gas therein and to convert gaseous ortho-hydrogen in the second hydrogen gas to gaseous para-hydrogen, thereby producing a third hydrogen gas comprising at least 50, 55, 60, 65, 70, 75, 80, 85, 90, or 95 mole percent gaseous para-hydrogen; 37. The system of any one of embodiments 31-36, further comprising: a condenser configured to receive a third hydrogen gas and generate liquid hydrogen from the third hydrogen gas, the condenser fluidly connected to the cryogenic vessel and configured to deliver liquid hydrogen to the cryogenic vessel.

[0153] Embodiment 39. The system of embodiment 38, wherein the airtight container is further configured to house a second para-hydrogen conversion catalyst therein, the second para-hydrogen conversion catalyst configured to convert gaseous ortho-hydrogen to gaseous para-hydrogen.

[0154] Embodiment 40. The system of embodiment 37 or 39, wherein the first or second para-hydrogen conversion catalyst comprises a material configured to adsorb liquid or gaseous ortho-hydrogen, split liquid or gaseous ortho-hydrogen, and release liquid or gaseous ortho-hydrogen.

[0155] Embodiment 41. The system of embodiment 37 or 39, wherein the liquid or gaseous ortho-hydrogen comprises two hydrogen spins, and the first or second para-hydrogen conversion catalyst comprises a paramagnetic material configured to break the symmetry between the two hydrogen spins, thereby converting the liquid or gaseous ortho-hydrogen to liquid or gaseous para-hydrogen.

[0156] Embodiment 42. The system of embodiment 37, 39, 40, or 41, wherein the first or second parahydrogen conversion catalyst comprises at least one material selected from the group consisting of gadolinium oxide, crude cerium oxide, neodymium oxide, FeCl2 on silica gel, paramagnetic Fe2O3 on porous glass, 2% paramagnetic Fe2O3 on porous glass, paramagnetic Fe2O3 on Florex, 15% paramagnetic Fe2O3 on Florex, ammonium ferric sulfate, magnetite, Fe3O4, Cr2O3 on alumina, paramagnetic Fe2O3 and Cr2O3 on alumina, 15% paramagnetic Fe2O3 and 9.3% Cr2O3 on alumina, Ni and thoria on alumina, 5.3% Ni and 0.24% thoria on alumina, MnO2 on silica gel, 18% MnO2 on silica gel, Ni on alumina, 0.5% Ni on alumina, hydrous manganese dioxide, hydrous ferric oxide, and hydrous iron oxide.

[0157] Embodiment 43. A method comprising: receiving liquid hydrogen; and boiling the liquid hydrogen, thereby forming a first hydrogen gas comprising at least 50, 55, 60, 65, 70, 75, 80, 85, 90, or 95 mole percent parahydrogen gas.

[0158] Embodiment 44 The method of embodiment 43, further comprising delivering a first hydrogen gas to the solution, the solution comprising precursors and catalysts to the target molecule.

[0159] Embodiment 45. The method of embodiment 44, further comprising using the first hydrogen gas to hydrogenate the precursor in the presence of a catalyst, thereby forming a target molecule.

[0160] Embodiment 46. The method of embodiment 45, wherein the precursor comprises a parahydrogen induced polarization (PHIP) precursor or a PHIP side-arm hydrogenation (PHIP-SAH) precursor.

[0161] Embodiment 47. The method of any one of embodiments 44 to 46, further comprising delivering a target molecule to the subject or sample, and obtaining a nuclear magnetic resonance (NMR) spectrum or a magnetic resonance imaging (MRI) image of the subject or sample in response to the target molecule.

[0162] Embodiment 48. The method of any one of embodiments 43-47, further comprising using a first para-hydrogen conversion catalyst configured to convert liquid ortho-hydrogen to liquid para-hydrogen.

[0163] 49. Obtaining a second hydrogen gas; converting the gaseous ortho-hydrogen in the second hydrogen gas to gaseous para-hydrogen, thereby producing a third hydrogen gas comprising at least 50, 55, 60, 65, 70, 75, 80, 85, 90, or 95 mole percent gaseous para-hydrogen; 48. The method of any one of embodiments 43-47, further comprising condensing the third hydrogen gas to produce liquid hydrogen from the third hydrogen gas.

[0164] Embodiment 50. The method of embodiment 49, further comprising converting the gaseous ortho-hydrogen to gaseous para-hydrogen using a second para-hydrogen conversion catalyst.

[0165] Embodiment 51. The method of embodiment 48 or 50, wherein the first or second para-hydrogen conversion catalyst comprises a material configured to adsorb liquid or gaseous ortho-hydrogen, split liquid or gaseous ortho-hydrogen, and release liquid or gaseous ortho-hydrogen.

[0166] Embodiment 52. The method of embodiment 48 or 50, wherein the liquid or gaseous ortho-hydrogen comprises two hydrogen spins, and the first or second para-hydrogen conversion catalyst comprises a paramagnetic material configured to break the symmetry between the two hydrogen spins, thereby converting the liquid or gaseous ortho-hydrogen to liquid or gaseous para-hydrogen.

[0167] Embodiment 53. The method of embodiment 48, 50, 51, or 52, wherein the first or second parahydrogen conversion catalyst comprises at least one material selected from the group consisting of gadolinium oxide, crude cerium oxide, neodymium oxide, FeCl2 on silica gel, paramagnetic Fe2O3 on porous glass, 2% paramagnetic Fe2O3 on porous glass, paramagnetic Fe2O3 on Florex, 15% paramagnetic Fe2O3 on Florex, ammonium ferric sulfate, magnetite, Fe3O4, Cr2O3 on alumina, paramagnetic Fe2O3 and Cr2O3 on alumina, 15% paramagnetic Fe2O3 and 9.3% Cr2O3 on alumina, Ni and thoria on alumina, 5.3% Ni and 0.24% thoria on alumina, MnO2 on silica gel, 18% MnO2 on silica gel, Ni on alumina, 0.5% Ni on alumina, hydrous manganese dioxide, hydrous ferric oxide, and hydrous iron oxide.

Claims

1. It is a system, A gas cylinder is provided, the gas cylinder is configured to contain hydrogen gas, the hydrogen gas contains parahydrogen gas at a first concentration of at least 45% and a maximum pressure of 40 bar, The parahydrogen gas has a decay time constant of at least 30 days. A system in which the para-hydrogen gas is used in para-hydrogen-induced polarization (PHIP), PHIP-side-arm hydrolysis (PHIP-SAH), signal amplification by reversible exchange (SABRE), or PHIP nuclear Overhauser effect system (PHIPNOESYS), nuclear magnetic resonance (NMR), or magnetic resonance imaging (MRI) procedures.

2. The system according to claim 1, wherein the first concentration is at least 95%.

3. The system according to claim 1, wherein the pressure is a maximum of 12 bar and the decay time constant is at least 30 days.

4. The system according to claim 1, wherein the pressure is a maximum of 3 bar and the decay time constant is at least 100 days.

5. The system according to claim 1, wherein the gas cylinder is purged by at least one purge operation so that the hydrogen gas contained therein is contained.

6. The system according to claim 5, wherein the at least one purging operation includes at least one part selected from the group consisting of at least one discharge operation, at least one heating operation, and at least one filling operation.

7. The gas cylinder and mixing chamber are further equipped with a first flow system fluid-connected to them. The first flow system is configured to direct the parahydrogen gas towards the mixing chamber, The mixing chamber is configured to contain the first solution within it. The first solution contains the target molecule or a derivative of the target molecule, The aforementioned target molecules are for use in the NMR or MRI procedure, The system according to claim 1, wherein the mixing chamber is configured to mix the parahydrogen gas with the target molecule or the derivative of the target molecule.

8. The system according to claim 7, wherein the mixing chamber is configured to mix the parahydrogen gas with the target molecule in the presence of a polarization transfer catalyst, thereby transferring spin order from the parahydrogen gas to the target molecule via SABRE interaction.

9. The system according to claim 7, wherein the derivative of the target molecule comprises at least one double or triple bond, and the mixing chamber is configured to mix the parahydrogen gas with the derivative of the target molecule in the presence of a hydrogenation catalyst, thereby inducing a parahydrogenation reaction between the parahydrogen gas and the derivative of the target molecule, thereby hydrogenating the at least one double or triple bond to form the target molecule, and transferring spin order from the parahydrogen gas to the target molecule via a PHIP interaction.

10. The system according to claim 7, wherein the derivative of the target molecule comprises at least one double bond or triple bond, and the mixing chamber is configured to mix the parahydrogen gas with the derivative of the target molecule in the presence of a hydrogenation catalyst, thereby inducing a parahydrogenation reaction between the parahydrogen gas and the derivative of the target molecule, thereby hydrogenating the at least one double bond or triple bond to form a parahydrogenated derivative of the target molecule.

11. The system further comprises a second flow system fluidly connected to the mixing chamber and the hydrolysis chamber, The second flow system is configured to direct the first solution containing the parahydrogenated derivative of the target molecule towards the hydrolysis chamber. The hydrolysis chamber is configured to contain the first solution containing the parahydrogenated derivative of the target molecule, The system according to claim 9, wherein the hydrolysis chamber is configured to mix the first solution containing the parahydrogenated derivative of the target molecule with a hydrolyzing agent, thereby hydrolyzing the parahydrogenated derivative of the target molecule, thereby forming hydrolyzed side arms and the target molecule via PHIP-SAH interactions.

12. The system further comprises a third flow system fluidly connected to the mixing chamber or the hydrolysis chamber and purification chamber, The system according to claim 7, wherein the third flow system is configured to direct the first solution containing the target molecule towards the purification chamber.

13. The system according to claim 12, wherein the purification chamber is configured to mix the first solution containing the target molecule with a second solution to form a third solution containing the target molecule, the third solution containing a contaminant at a reduced concentration compared to the first solution.

14. The system according to claim 13, wherein the purification chamber is configured to carry out a precipitation reaction with respect to the first solution containing the target molecule, thereby forming a precipitate of the target molecule, and to mix the precipitate of the target molecule with a second solution, thereby forming a third solution containing the target molecule, the third solution containing a reduced concentration of contaminants compared to the first solution.

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