Systems and methods for producing hyperpolarized materials

Abstract

Systems and methods for containing parahydrogen are disclosed. In some systems and methods, a gas cylinder is configured to contain hydrogen therein. The hydrogen may include a parahydrogen gas at a first concentration of at least 45% and a pressure of at most 40 bar. The parahydrogen gas may have a decay time constant of at least 30 days. The parahydrogen gas can be used in PHIP, PHIP-SAH, SABRE or PHIP NOESYS NMR or MRI experiments. In some systems and methods, a low temperature chamber is configured to contain liquid hydrogen therein. The liquid hydrogen may include liquid parahydrogen at a concentration of at least 50 mol%. The liquid hydrogen may be boiled to produce hydrogen containing at least 50 mol% parahydrogen gas. The parahydrogen gas can be used in PHIP, PHIP-SAH, SABRE or PHIP NOESYS NMR or MRI experiments.

Description

[0001] Cross-reference to related applications

[0002] This application claims priority to U.S. Provisional Patent Application No. 63 / 364,268, filed on May 6, 2022, entitled “Parahydrogen gas obtained from liquid hydrogen,” which is incorporated herein by reference in its entirety for all purposes. Technical Field

[0003] The disclosed embodiments generally relate to the generation of hyperpolarized materials for use in nuclear magnetic resonance (NMR), magnetic resonance imaging (MRI), or similar applications. Background Art

[0004] Nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) are techniques with important applications in chemistry, biology, and medical imaging. Despite these successes, it is recognized that magnetic resonance applications may be limited by the small nuclear polarization of the analyte (typically on the order of 10 -5 This small nuclear polarization may result in limited sensitivity compared to other analytical techniques such as mass spectrometry.

[0005] Increasing nuclear spin polarization to exceed its thermal equilibrium value can greatly improve magnetic resonance sensitivity. Known techniques such as parahydrogen induced polarization (PHIP), PHIP-sidearm hydrogenation (PHIP-SAH) and signal amplification (SABRE) by reversible exchange can be used to increase nuclear spin polarization. Using such techniques, the nuclear spin polarization of a material can be increased by 10,000 times or more. Enhanced nuclear spin polarization can lead to a proportional increase in NMR / MRI signals. Although this enhanced polarization decays over time due to the relaxation time of the nuclear spins in the polarized molecules, for many molecules, the relaxation time can be on the order of seconds to minutes, during which the increased polarization can lead to a significant increase in NMR / MRI signal sensitivity. By achieving such a significant increase in NMR / MRI signal sensitivity, increased nuclear spin polarization can achieve new applications, such as using metabolites with increased nuclear spin polarization in MRI scanners to image in vivo metabolism, accelerate NMR spectroscopy studies, and make it possible to visualize previously unseen molecular dynamics and structures. Summary of the invention

[0006] According to the present disclosure, hydrogen containing parahydrogen gas can be contained in a gas cylinder at a relatively low pressure and optionally a relatively low volume. Then, in nuclear magnetic resonance imaging (NMR) or magnetic resonance imaging (MRI) experiments, end users such as hospitals or clinics can use parahydrogen gas. For example, parahydrogen gas can be used by end users in parahydrogen induced polarization (PHIP), PHIP-sidearm hydrolysis (PHIP-SAH), signal amplification (SABRE) by reversible exchange, or PHIP nuclear Overhauser effect system (PHIPNOESYS) experiments. Relatively low pressure can allow parahydrogen gas to decay into positive hydrogen at a relatively low rate, thereby allowing enough time for the gas cylinder to be transported to the end user, and allowing the end user to use parahydrogen gas in PHIP, PHIP-SAH, SABRE or PHIPNOESYS experiments. The combination of relatively low pressure and optionally relatively low volume can alleviate the safety issues associated with using flammable gas under high pressure.

[0007] According to the present disclosure, liquid hydrogen containing a high percentage of liquid parahydrogen can be generated and contained in a cryogenic container. The liquid hydrogen can then be boiled to obtain hydrogen containing a high percentage of parahydrogen gas. Then, in NMR or MRI experiments, end users such as hospitals or clinics can use the parahydrogen gas. In some cases, liquid hydrogen can be stored at a central distribution facility such as a supply station. Liquid hydrogen can be boiled and used to fill gas cylinders or other gas tanks with hydrogen containing a high percentage of parahydrogen gas. Then, end users can use the parahydrogen gas. For example, in PHIP, PHIP-SAH, SABRE or PHIPNOESYS experiments, end users can use parahydrogen gas. Since the service life of liquid parahydrogen is very long, the use of liquid hydrogen containing a high percentage of liquid parahydrogen can allow the shelf life of the parahydrogen source to be greatly extended, and the supply chain logistics associated with distributing parahydrogen to end users can be significantly simplified.

[0008] The 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 a pressure of at most 20 bar. The parahydrogen gas may have a decay time constant of at least 30 days. The parahydrogen gas may be used in a PHIP, PHIP-SAH, SABRE, or PHIPNOESYS NMR or MRI experiment.

[0009] The disclosed embodiments include a method for containing parahydrogen gas. The method may include containing hydrogen gas in a gas cylinder. The hydrogen gas may include parahydrogen gas at a first concentration of at least 45% and a pressure of at most 20 bar. The parahydrogen gas may have a decay time constant of at least 30 days. The parahydrogen gas may be used in a PHIP, PHIP-SAH, SABRE, or PHIPNOESYS NMR or MRI experiment.

[0010] The disclosed embodiments include a system for generating parahydrogen gas. The system may include a cryogenic container. The cryogenic container may be configured to contain liquid hydrogen therein. The system may include a chamber fluidly coupled to a cryogenic chamber. The chamber may be configured to receive liquid hydrogen from the cryogenic container. The chamber may be configured to boil the received liquid hydrogen and thereby form a first hydrogen gas containing at least 50 mole percent (mol %) parahydrogen gas. The parahydrogen gas may be used in a PHIP, PHIP-SAH, SABRE, or PHIPNOESYS NMR or MRI experiment.

[0011] The disclosed embodiments include a method for generating parahydrogen gas. The method may include receiving liquid hydrogen and boiling the liquid hydrogen to form a first hydrogen gas containing at least 50 mol% parahydrogen gas. The parahydrogen gas may be used in a PHIP, PHIP-SAH, SABRE, or PHIPNOESYS NMR or MRI experiment.

[0012] 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. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] The accompanying drawings, which comprise a part of this specification, illustrate several embodiments and, together with the description, serve to explain the principles and features of the disclosed embodiments. In the drawings:

[0014] Figure 1 A first exemplary system for providing parahydrogen gas for use in parahydrogen induced polarization (PHIP), PHIP-sidearm hydrolysis (PHIP-SAH), signal amplification by reversible exchange (SABRE), or PHIP nuclear Overhauser effect system (PHIPNOESYS) applications is depicted in accordance with the disclosed embodiments.

[0015] Figure 2 An exemplary decay curve is depicted showing the relationship between the parahydrogen shelf life of hydrogen gas containing 95% of the initial parahydrogen concentration and the hydrogen pressure according to the disclosed embodiments.

[0016] Figure 3Exemplary decay curves showing the shelf life of parahydrogen under various cylinder purge conditions are shown in accordance with disclosed embodiments.

[0017] Figure 4 A first exemplary method for providing parahydrogen gas for use in PHIP, PHIP-SAH, SABRE, or PHIPNOESYS applications is depicted in accordance with the disclosed embodiments.

[0018] Figure 5A A second exemplary system for providing parahydrogen gas for use in PHIP, PHIP-SAH, SABRE, or PHIPNOESYS applications is depicted in accordance with the disclosed embodiments.

[0019] Figure 5B A third exemplary system for providing parahydrogen gas for use in PHIP, PHIP-SAH, SABRE, or PHIPNOESYS applications is depicted in accordance with the disclosed embodiments.

[0020] Fig. 6A A second exemplary method for providing parahydrogen gas for use in PHIP, PHIP-SAH, SABRE, or PHIPNOESYS applications is depicted in accordance with the disclosed embodiments.

[0021] Figure 6B A third exemplary method for providing parahydrogen gas for use in PHIP, PHIP-SAH, SABRE, or PHIPNOESYS applications is depicted in accordance with the disclosed embodiments.

[0022] Figure 7 Depicted is an exemplary Raman spectrum of a hydrogen gas mixture containing more than 90% parahydrogen generated from liquid hydrogen according to disclosed embodiments. DETAILED DESCRIPTION

[0023] Reference will now be made in detail to the exemplary embodiments discussed with respect to the accompanying drawings. In some cases, the same reference numerals will be used throughout the accompanying drawings and the following description to refer to the same or similar parts. Unless otherwise defined, technical and / or scientific terms have the meanings commonly understood by those of ordinary skill in the art. The disclosed embodiments are described in sufficient detail to enable those skilled in the art to practice the disclosed embodiments. It should be understood that other embodiments may be utilized and may be changed without departing from the scope of the disclosed embodiments. Therefore, materials, methods, and examples are merely illustrative and are not intended to necessarily limit.

[0024] NMR and MRI can be used in a variety of applications, including but not limited to determining chemical structures in synthetic intermediates, determining atomic-level structures 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, due to the combination of the tiny size of the nuclear magnetic resonance magnetic moment and the corresponding small polarization at thermal equilibrium, NMR and MRI can have limited sensitivity. This limited sensitivity may hinder the use of NMR and MRI in some applications, and may make other applications of NMR and MRI impractically time-consuming or material-intensive.

[0025] NMR and MRI sensitivity can be increased by using higher magnetic fields and optimized detection systems. However, an alternative approach is to increase NMR and MRI sensitivity by increasing nuclear spin polarization to levels significantly greater 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 an optimized detection system.

[0026] Various techniques can be used to increase nuclear spin polarization, 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 referred to herein as 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.

[0027] For example, recent work in NMR and MRI has demonstrated that NMR and MRI signals associated with various biologically relevant imaging agents can be enhanced by many orders of magnitude using PHIP or PHIP-SAH. Such dramatic signal enhancement allows spectroscopic analysis of biologically relevant imaging agents as they are metabolized by various tissues at different locations in the body. Analysis of metabolic information determined by such spectral imaging can allow non-invasive determination of the health status of tissues in the body. For example, abnormal metabolism of biologically relevant imaging agents may indicate diseases at some locations in the body, such as cancer.

[0028] In PHIP and PHIP-SAH, a derivative (e.g., a precursor) of a related molecule is reacted with parahydrogen to form a parahydrogenated form of the derivative. Then, the spin order is transferred from the proton added via the parahydrogenation reaction to the related nucleus (e.g., carbon-13 nucleus) contained in the related molecule. In PHIP, the parahydrogenated form of the derivative is chemically identical to the related molecule and is distinguished from the related molecule only by the spin order derived from the parahydrogenation reaction. In PHIP-SAH, the parahydrogenated form of the derivative is cracked (e.g., hydrolyzed) to produce hyperpolarized related molecules. In SABRE, the related molecule itself forms a coordination complex with a polarization transfer catalyst and parahydrogen. Then the spin order is transferred from parahydrogen to the related nucleus in the related molecule via the coordination complex. Then the related molecule is optionally purified and used for NMR or MRI procedures. PHIPNOESYS utilizes PHIP or PHIP-SAH to generate a hyperpolarized material (e.g., a source compound), and polarization is transferred from the source compound to the material (e.g., a target compound, a target molecule, or a related molecule) used in the NMR spectrum. Polarization transfer from source compounds to target compounds occurs via the intermolecular Nuclear Overhauser Effect (NOE). PHIPNOESYS has been shown to increase the signal in NMR spectra by nearly 2,000-fold, allowing NMR spectroscopy to be applied at significantly lower concentrations than would otherwise be achievable.

[0029] Each of PHIP, PHIP-SAH, SABRE and PHIPNOESYS requires a parahydrogen source that acts as a source of spin order, which allows hyperpolarization of the relevant nuclei. High concentrations of parahydrogen are usually produced by cooling gaseous hydrogen (e.g., cooling to a temperature below 77 Kelvin (K), 25K or lower) in the presence of a paramagnetic catalyst. At room temperature, gaseous hydrogen contains about 25% parahydrogen (which can be used for PHIP, PHIP-SAH, SABRE and PHIPNOESYS) and about 75% orthohydrogen (which is not suitable for PHIP, PHIP-SAH, SABRE and PHIPNOESYS). At significantly colder temperatures, orthohydrogen is converted into parahydrogen, thereby increasing the concentration of parahydrogen in hydrogen (e.g., the concentration of parahydrogen is about 50% at 77K and greater than 98% at 25K). In most current studies, the hydrogen is then heated and used immediately in a PHIP, PHIP-SAH, SABRE, or PHIPNOESYS experiment, or stored in high-pressure cylinders for later use in such experiments.

[0030] As PHIP, PHIP-SAH, SABRE, and PHIPNOESYS enter more routine use, such as in clinical applications, it will be necessary for end users such as hospitals or clinics to have access to a reliable source of parahydrogen gas. However, due to safety issues associated with low temperatures, high pressures, and the use of highly flammable gases such as hydrogen, it is difficult for such end users to purchase and maintain the equipment required to produce parahydrogen on site. High pressure and flammability issues also apply to the idea of ​​transporting high-pressure cylinders filled with parahydrogen gas to such end users. In addition, under high pressure, parahydrogen is easily converted to orthohydrogen, which requires the end user to use its parahydrogen supply quickly. Therefore, it is also not ideal to transport high-pressure cylinders filled with parahydrogen to end users. Therefore, new systems and methods are needed that allow parahydrogen to be transported to end users while alleviating safety and time issues.

[0031] The disclosed embodiments contain hydrogen gas containing parahydrogen in a gas cylinder at a relatively low pressure and optionally a relatively low volume. Then, in an NMR or MRI experiment, an end user, such as a hospital or clinic, can use the parahydrogen gas. For example, in a PHIP, PHIP-SAH, SABRE, or PHIPNOESYS experiment, the end user can use the parahydrogen gas. The relatively low pressure can allow the parahydrogen gas to decay into positive hydrogen at a relatively low rate, thereby allowing enough time to transport the gas cylinder to the end user, and allowing the end user to use the parahydrogen gas in a PHIP, PHIP-SAH, SABRE, or PHIPNOESYS experiment. The combination of relatively low pressure and optionally relatively low volume can alleviate safety issues associated with the use of flammable gases at high pressure. As described herein, the disclosed embodiments can be used for polarization-related molecules.

[0032] The disclosed embodiments generate and contain liquid hydrogen containing a high percentage of liquid parahydrogen in a cryogenic container. The liquid hydrogen can then be boiled to obtain hydrogen containing a high percentage of parahydrogen gas. The parahydrogen gas can then be used by an end user, such as a hospital or clinic, in an NMR or MRI experiment. In some cases, the liquid hydrogen can be stored at a central distribution facility, such as a supply 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 a gas cylinder or other gas tank with hydrogen containing a high percentage of parahydrogen gas. The parahydrogen gas can then be used by an end user. For example, in a PHIP, PHIP-SAH, SABRE, or PHIPNOESYS experiment, the end user can use the parahydrogen gas. Since the service life of liquid parahydrogen is very long, the use of liquid hydrogen containing a high percentage of liquid parahydrogen can allow the shelf life of the parahydrogen source to be greatly extended, and can significantly simplify the supply chain logistics associated with distributing parahydrogen to end users.

[0033] Hyperpolarization and Parahydrogen

[0034] As used in this disclosure, "polarization" refers to the imbalance in the orientation of electron or nuclear spins. In some embodiments, 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, given 200,000 1 For H nuclear spins, a 2% polarization may correspond to 102,000 spins in a first direction and 98,000 spins in the opposite direction. In some embodiments, "hyperpolarization" may include polarization of a species (e.g., nuclei, electrons, etc.) that exceeds the typical polarization level of that species observed in thermal equilibrium when exposed to a particular magnetic field. As a non-limiting example, a 1 T magnetic field in thermal equilibrium may correspond to 102,000 spins in a first direction and 98,000 spins in the opposite direction. 1 A sample with a H nuclear spin polarization exceeding 0.000341% can be hyperpolarized to have a much higher (e.g., at least one or more orders of magnitude higher) thermal equilibrium polarization than 0.000341%. 1 H nuclear spin polarization. As another non-limiting example, in a 3T magnetic field in thermal equilibrium 13 A sample with a C spin polarization exceeding 0.000257% can be hyperpolarized. As another non-limiting example, a sample in a 3T magnetic field at thermal equilibrium 15 Samples with N spin polarization exceeding 0.000103% can be hyperpolarized.

[0035] As used in this disclosure, "hyperpolarization" describes a condition in which the absolute value of the difference between the spin state population (e.g., nuclear spin state, proton spin state, etc.) in one state (e.g., spin up) and the spin state population in another state (e.g., spin down) exceeds the absolute value of the corresponding difference in thermal equilibrium.

[0036] Consistent with the disclosed embodiments, parahydrogen can be used as a polarization source. As described herein, parahydrogen is a form of molecular hydrogen in which two proton spins are in a singlet state. The disclosed embodiments are not limited to a specific method for producing parahydrogen. Parahydrogen can be formed in gaseous form or liquid form. In some embodiments, parahydrogen in gaseous form is produced by flowing hydrogen through a chamber with a catalyst (e.g., iron oxide or another suitable catalyst) at low temperatures. Hydrogen can contain both parahydrogen and orthohydrogen. Low temperatures can cause hydrogen to reach thermodynamic equilibrium indoors, thereby increasing the parahydrogen population.

[0037] As used in the present 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, at most 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.

[0038] Hydrogen can exhibit a population difference between proton spin states that greatly exceeds the population difference between proton spin states in thermal equilibrium. Hydrogen containing a high concentration of parahydrogen can have a large population difference between a singlet spin state and any triplet spin state. In the case of Iz1Iz2, for example, there is a large population difference between the spin state |↑>|↓> and the spin state |↑>|↑>. The population difference of the proton spin state can be at least about 0.1 (for example, a 10% difference in spin state 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, at most about 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1 or less, or within the range defined by any two of the aforementioned values.

[0039] System for providing low pressure parahydrogen gas

[0040] Figure 1 A first exemplary system 100 for providing parahydrogen gas for use in PHIP, PHIP-SAH, SABRE, or PHIPNOESYS NMR or MRI applications according to the disclosed embodiments is depicted. In the illustrated example, the system 100 includes a gas cylinder 110. In some embodiments, the gas cylinder 110 is configured to contain hydrogen gas therein. In some embodiments, the gas cylinder 110 contains hydrogen gas therein.

[0041] In some embodiments, the hydrogen gas comprises a first concentration of parahydrogen gas. 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 at most 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 foregoing values. For example, in some embodiments, the first concentration is between about 45% and about 99.9%, about 45% and about 99.5%, about 45% and about 99%, about 45% and about 95%, about 45% and about 90%, about 50% and about 99.9%, about 50% and about 99.5%, about 50% and about 99%, about 50% and about 95%, about 50% and about 90%, etc. In some embodiments, the first concentration is measured as a fractional percentage of hydrogen molecules in the parahydrogen state. For example, a first concentration of 45% means that 45% of the hydrogen molecules are in the parahydrogen state and 55% of the hydrogen molecules are in the orthohydrogen state. The first concentration can be measured on a volume / volume (v / v), weight / weight (w / w), molar percentage (mol%), or another basis.

[0042] In some embodiments, the hydrogen 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 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 comprises a pressure within a range defined by any two of the aforementioned values. For example, in some embodiments, the hydrogen gas comprises a range between about 1 bar and about 40 bar, about 1 bar and about 35 bar, about 1 bar and about 30 bar, about 1 bar and about 30 bar, about 1 bar and about 20 bar, about 1 bar and about 15 bar, about 1 bar and about 10 bar, about 1 bar and about 5 bar, about 1 bar and about 4 bar, about 1 bar and about 3 bar, about 1 bar and about 2 bar, about 2 bar and about 40 bar, about 2 bar and about 35 bar, about 2 bar and about 30 bar, about 2 bar and about 25 bar, about 2 bar and about 20 bar. bar, about 2 bar and about 15 bar, about 2 bar and about 10 bar, about 2 bar and about 5 bar, about 2 bar and about 4 bar, about 2 bar and about 3 bar, about 3 bar and about 40 bar, about 3 bar and about 35 bar, about 3 bar and about 30 bar, about 3 bar and about 25 bar, about 3 bar and about 20 bar, about 3 bar and about 15 bar, about 3 bar and about 10 bar, about 3 bar and about 5 bar, about 3 bar and about 4 bar, about 4 bar and about 40 bar, about 4 bar and about 35 bar, about 4 bar and about 30 bar, about 4 bar and about 20 bar , about 4 bar and about 20 bar, about 4 bar and about 15 bar, about 4 bar and about 10 bar, about 4 bar and about 5 bar, about 5 bar and about 40 bar, about 5 bar and about 35 bar, about 5 bar and about 30 bar, about 5 bar and about 25 bar, about 5 bar and about 20 bar, about 5 bar and about 15 bar, about 5 bar and about 10 bar, about 10 bar and about 40 bar, about 10 bar and about 35 bar, about 10 bar and about 30 bar, about 10 bar and about 25 bar, about 10 bar and about 20 bar, about 10 bar and about 15 bar, about 15 bar and about 40 bar, about 15 bar and about 35 bar, about 15 bar and about 30 bar, about 15 bar and about 25 bar, about 15 bar and about 20 bar, about 20 bar and about 40 bar, about 20 bar and about 35 bar, about 20 bar and about 30 bar, about 20 bar and about 25 bar, about 25 bar and about 40 bar, about 25 bar and about 35 bar, about 25 bar and about 30 bar, about 30 bar and about 40 bar, about 30 bar and about 35 bar, about 35 bar and about 40 bar, and so on.

[0043] In some embodiments, the hydrogen gas has a volume of at most about 250, 240, 230, 220, 210, 200, 190, 180, 170, 160, 150, 140, 130, 120, 110, 100, 95, 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 35, 30, 25, 20, 15, 10, 5, 1, or less. In some embodiments, the hydrogen has a volume of at least 1 standard liter, 5 standard liters, 10 standard liters, 15 standard liters, 20 standard liters, 25 standard liters, 30 standard liters, 35 standard liters, 40 standard liters, 45 standard liters, 50 standard liters, 55 standard liters, 60 standard liters, 65 standard liters, 70 standard liters, 75 standard liters, 80 standard liters, 85 standard liters, 90 standard liters, 95 standard liters, 100 standard liters, 110 standard liters, 120 standard liters, 130 standard liters, 140 standard liters, 150 standard liters, 160 standard liters, 170 standard liters, 180 standard liters, 190 standard liters, 200 standard liters, 210 standard liters, 220 standard liters, 230 standard liters, 240 standard liters, 250 standard liters or more. In some embodiments, the hydrogen has a volume within a range defined by any two of the foregoing values.

[0044] 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 within the range defined by any two of the foregoing values. In some embodiments, the decay time constant represents the decay time constant for converting parahydrogen molecules into orthhydrogen molecules. In some embodiments, the decay time constant is given by the decay equation C(t)-C 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).

[0045] Figure 2 An exemplary decay curve is depicted showing the relationship between the parahydrogen shelf life and the hydrogen pressure for hydrogen gas containing 95% of the initial parahydrogen concentration according to the disclosed embodiments. shelf is arbitrarily defined as the amount of time required for the parahydrogen concentration to decrease from its initial 95% concentration to its final 85% concentration. That is, like Figure 2As shown, the shelf life decreases rapidly with increasing hydrogen pressure. Therefore, in some embodiments, a relatively low pressure can allow the parahydrogen gas to decay into orthohydrogen at a relatively low rate, thereby allowing sufficient time to transport the cylinder to the end user and allowing the end user (e.g., a hospital or clinic) to use the parahydrogen gas in a PHIP, PHIP-SAH, SABRE, or PHIPNOESYS experiment. In addition, the combination of relatively low pressure and optionally relatively low volume can alleviate safety issues associated with using flammable gases at high pressures, thereby greatly simplifying the logistics of supplying parahydrogen to end users for their PHIP, PHIP-SAH, SABRE, or PHIPNOESYS experiments.

[0046] return Figure 1 In some embodiments, the gas cylinder 110 has been purged by at least one purging operation before containing the hydrogen therein. In some embodiments, the at least one purging 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 a rotary pump, a vortex pump, a cryogenic pump, a turbomolecular pump, an ion pump, an aspirator pump, etc.

[0047] In some embodiments, the at least one purging operation comprises at least one heating operation. In some embodiments, the at least one heating operation comprises heating the gas cylinder 110. In some embodiments, the gas cylinder 110 is heated to a temperature of at least about 30 degrees Celsius (°C), 40°C, 50°C, 60°C, 70°C, 80°C, 90°C, 100°C, or more, at most about 100°C, 90°C, 80°C, 70°C, 60°C, 50°C, 40°C, 30°C, or less, or a temperature within a range defined by any two of the foregoing values. In some embodiments, the at least one heating operation is performed before, during, or after the at least one evacuation operation.

[0048] In some embodiments, the at least one purging operation comprises 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 comprises an inert gas, such as nitrogen or argon. In some embodiments, the at least one gas comprises hydrogen. In some embodiments, the at least one gas comprises hydrogen with an increased parahydrogen concentration when 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, at most about 99.9999%, 99.9995%, 99.999%, 99.9995%, 99.999%, 99.995%, 99.999%, 99.95%, 99.9%, 99.9%, 99.5%, 99%, 95% or less, or a purity within a range 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 evacuation operation or the at least one heating operation. In some embodiments, the at least one filling operation is performed by ventilating the gas cylinder 110 .

[0049] In some embodiments, the at least one purge operation reduces the concentration of impurities or contaminants within the gas cylinder 110 before filling the gas cylinder 110 with hydrogen gas containing parahydrogen. In some embodiments, the at least one purge operation reduces the concentration of oxygen, nitrogen, trace gases such as carbon dioxide, water vapor, etc.

[0050] In some embodiments, the gas cylinder 110 has been purged with 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 in the gas cylinder 110. In some embodiments, the gas cylinder 110 has been purged with at most 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 in the gas cylinder 110. In some embodiments, the gas cylinder 110 has been purged with a plurality of purge operations within a range defined by any two of the foregoing values ​​prior to containing hydrogen gas in the gas cylinder 110.

[0051] Figure 3 Exemplary decay curves according to the disclosed embodiments are shown, which show the parahydrogen shelf life under various cylinder purge conditions. The cylinder was evacuated using a vacuum pump, subjected to various purge conditions, and filled with hydrogen containing 90% of the initial parahydrogen concentration. The purge conditions were: (1) untreated (no heating or filling operation) ( Figure 3(2) four alternating cycles of evacuation (using a turbomolecular pump) and filling ( Figure 3 ) and (3) more than 10 alternating cycles of evacuation (using a turbomolecular pump) and filling ( Figure 3 ">10 purge cycles"). Figure 3 As shown, the decay constants are: (1) 17.8 ± 3 days, (2) 22.9 ± 1.8 days, and (3) 35.5 ± 0.4 days. Therefore, purging the cylinder before filling with hydrogen can greatly improve the lifetime of parahydrogen.

[0052] return Figure 1 In some embodiments, the system 100 further comprises a parahydrogen generating device ( Figure 1 ). In some embodiments, during the filling of the gas cylinder 110 with hydrogen, a parahydrogen gas generating device is coupled to the gas cylinder 110. In some embodiments, the parahydrogen generating device is configured to generate hydrogen gas comprising any first concentration of parahydrogen gas described herein. In some embodiments, the parahydrogen generating device comprises a parahydrogen generating device as described in WO2022157534, which is incorporated herein by reference in its entirety for all purposes.

[0053] 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 the 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 the flow rate of the parahydrogen gas flowing 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 the pressure of the parahydrogen gas above the pressure of the parahydrogen gas supplied 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 can be used for the PHIP, PHIP-SAH, SABRE, or PHIPNOESYS procedures.

[0054] In some embodiments, the system 100 further includes 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 the 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.

[0055] In some embodiments, the first solution is configured to generate related molecules for use in PHIP or PHIP-SAH experiments. In such embodiments, the first solution comprises related molecules or derivatives (e.g., precursors) of related molecules. In some embodiments, the related molecules are used in NMR or MRI procedures. In some embodiments, the mixing chamber 130 is configured to mix parahydrogen gas with related molecules or derivatives of related molecules. In some embodiments, the related molecules comprise any biologically relevant contrast agent described herein.

[0056] In some embodiments, the mixing chamber 130 is configured to mix the parahydrogen gas into the first solution so that the parahydrogen gas is mixed with the related molecules. In some embodiments, the first solution contains a polarization transfer catalyst, such as [IrCl(COD)(IMes)], where COD is cis, cis-1,5-cyclobutadiene, and IMes is 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene. In some embodiments, the parahydrogen gas is mixed with the related molecules in the presence of the polarization transfer catalyst. In some embodiments, in the presence of the polarization transfer catalyst, the mixture of the parahydrogen gas and the related molecules transfers the spin order from the parahydrogen gas to the related molecules via SABRE interactions.

[0057] In some embodiments, the derivative of the related molecule comprises at least one double bond or triple bond. In some embodiments, the mixing chamber 130 is configured to mix the parahydrogen gas into the first solution so that the parahydrogen gas mixes with the derivative of the related molecule. In some embodiments, the first solution contains a hydrogenation catalyst. In some embodiments, the parahydrogen gas is mixed with the derivative of the related molecule in the presence of the hydrogenation catalyst. In some embodiments, in the presence of the hydrogenation catalyst, the mixture of the parahydrogen gas and the derivative of the related molecule induces a parahydrogenation reaction between the parahydrogen gas and the derivative of the related molecule.

[0058] In some embodiments, the parahydrogenation reaction hydrogenates at least one double bond or triple bond and forms related molecules. In some embodiments, the spin order from the parahydrogen gas is transferred to the related molecules via PHIP interaction. Examples of PHIP interactions can be found in, for example, WO2022157534 and WO2022018514, each of which is incorporated herein by reference in its entirety for all purposes.

[0059] In some embodiments, the secondary hydrogenation reaction hydrogenates at least one double bond or triple bond and forms a secondary hydrogenated derivative of the related molecule. In some embodiments, the secondary hydrogenated derivative of the related molecule is mixed with a hydrolyzing agent such as sodium hydroxide (NaOH) or potassium hydroxide (KOH). In some embodiments, the hydrolyzing agent hydrolyzes the secondary hydrogenated derivative of the related molecule, thereby forming a hydrolyzed side arm and related molecules via PHIP-SAH interactions. Examples of PHIP-SAH interactions can be found in, for example, WO2022157534, WO2022018514, and WO2021198776, each of which is incorporated herein by reference in its entirety for all purposes.

[0060] 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 tubes, liquid flow pumps, and / or liquid flow valves configured to determine a flow rate at which the first solution flows from the mixing chamber 130.

[0061] In some embodiments, system 100 further comprises a hydrolysis chamber 150. In some embodiments, second flow system 140 is configured to direct the first solution to hydrolysis chamber 150. In some embodiments, hydrolysis chamber 150 is configured to receive the first solution after the first solution flows through second flow system 140 to hydrolysis chamber 150. In some embodiments, hydrolysis chamber 150 is configured to mix the first solution with a hydrolysis agent, thereby hydrolyzing the para-hydrogenated derivative of the molecule of interest.

[0062] Despite Figure 1 1 and 10. Although depicted as utilizing the second flow system 140 to flow the first solution to the hydrolysis chamber 150, the system 100 need not be configured in this manner. For example, the second flow system 140 can be configured to direct the hydrolysis agent to the mixing chamber 130, and the hydrolysis chamber 150 can be omitted. In this case, the hydrolysis agent flows to the mixing chamber 130, and the hydrolysis of the secondary hydrogenated derivatives of the molecules of interest occurs in the mixing chamber 130.

[0063] 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 tubes, 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.

[0064] 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 hold the first solution after the first solution flows to the purification chamber 170 through the third flow system 160. In some embodiments, the purification chamber 170 is configured to mix the first solution with the second solution to form a third solution containing molecules of interest. In some embodiments, the third solution comprises a reduced concentration of contaminants compared to the first solution.

[0065] 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 related molecules. In some embodiments, the purification chamber 170 is configured to mix the precipitate with the second solution to form a third solution. Examples of precipitation reactions are described in, for example, WO2022018514 and WO2022269350, each of which is incorporated herein by reference in its entirety for all purposes.

[0066] Despite Figure 1 1 is depicted as flowing the first solution to the purification chamber 170 using the third flow system 160, but the system 100 need not be configured in this manner. For example, the third flow system 160 can be configured to direct the second solution to the hydrolysis chamber 150, and the purification chamber 170 can be omitted. In this case, the second solution flows to the hydrolysis chamber 150, and the purification of the molecules of interest occurs in the hydrolysis chamber 150. Alternatively, the third flow system 160 can be configured to direct the second solution to the mixing chamber 130, and both the hydrolysis chamber 150 and the purification chamber 170 can be omitted. In this case, the second solution flows to the mixing chamber 130, and the purification of the molecules of interest occurs in the mixing chamber 130.

[0067] In some embodiments, the system 100 is configured to implement Figure 4 The method 400 is described.

[0068] Method for providing low pressure parahydrogen gas

[0069] Figure 4 A first exemplary method 400 is depicted for providing parahydrogen gas for use in PHIP, PHIP-SAH, SABRE, or PHIPNOESYS NMR or MRI applications in accordance with the disclosed embodiments. Figure 1 The system 100 performs the method 400 .

[0070] At step 410, hydrogen gas is contained within a gas cylinder. In some embodiments, the hydrogen gas comprises any first concentration of parahydrogen 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 used 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.

[0071] At step 420, the parahydrogen gas is mixed with any of the first solutions described herein. In some embodiments, the pressure of the parahydrogen gas is increased above the pressure of the parahydrogen gas supplied by the cylinder prior to mixing the parahydrogen gas with the first solution.

[0072] In some embodiments, parahydrogen gas is mixed with any of the related molecules 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 related molecules via SABRE interactions, as described herein. In some embodiments, the related molecules comprise any of the related molecules described herein.

[0073] In some embodiments, parahydrogen gas is mixed with any derivative of any related molecule 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 related molecule. In some embodiments, the parahydrogenation reaction hydrogenates at least one double bond or triple bond of the derivative of the related molecule to form a related molecule, and transfers spin order from the parahydrogen gas to the related molecule via a PHIP interaction as described herein.

[0074] In some embodiments, in the presence of any hydrogenation catalyst described herein, parahydrogen gas is mixed with derivatives of related molecules. In some embodiments, such mixing induces a parahydrogenation reaction between parahydrogen gas and derivatives of related molecules. In some embodiments, the parahydrogenation reaction hydrogenates at least one double bond or triple bond of the derivative of the related molecule, and forms a parahydrogenated derivative of the related molecule. In some embodiments, the first solution containing the parahydrogenated derivative of the related molecule is mixed with any hydrolyzing agent described herein. In some embodiments, the hydrolyzing agent hydrolyzes the parahydrogenated derivative of the related biomolecule, and thereby forms a hydrolyzed side arm and related molecules via the PHIP-SAH interaction as described herein.

[0075] In some embodiments, the first solution is purified at step 430. In some embodiments, the first solution is purified using any of the purification methods described herein. For example, in some embodiments, purifying the first solution comprises mixing the first solution with the second solution to form a third solution containing the molecules of interest, as described herein. In some embodiments, the third solution comprises a reduced concentration of contaminants compared to the first solution, as described herein. In some embodiments, purifying the first solution comprises performing a precipitation reaction on the first solution to form a precipitate of the molecules of interest, and mixing the precipitate of the molecules of interest with the second solution to form a third solution containing the molecules of interest, as described herein.

[0076] System for producing parahydrogen gas from liquid parahydrogen

[0077] Figure 5A A second exemplary system 500A is depicted for providing parahydrogen gas for use in PHIP, PHIP-SAH, SABRE, or PHIPNOESYS applications in accordance with the 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 contains 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 of liquid parahydrogen. In some embodiments, the liquid hydrogen contains at most about 95 mol%, 90 mol%, 85 mol%, 80 mol%, 75 mol%, 70 mol%, 65 mol%, 60 mol%, 55 mol%, 50 mol% or less of liquid parahydrogen. In some embodiments, the liquid hydrogen contains liquid parahydrogen in an amount within a range defined by any two of the aforementioned values.

[0078] In some embodiments, the cryogenic container 510 comprises a volume of at least about 1 liter (L), 2L, 3L, 4L, 5L, 6L, 7L, 8L, 9L, 10L, 20L, 30L, 40L, 50L, 60L, 70L, 80L, 90L, 100L, 200L, 300L, 400L, 500L, 600L, 700L, 800L, 900L, 1,000L, or more. In some embodiments, cryogenic container 510 comprises a volume of at most 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, cryogenic container 510 comprises a volume within a range defined by any two of the foregoing values.

[0079] In some embodiments, the cryogenic container 510 includes a first container and a second container. In some embodiments, the first container is configured to contain liquid hydrogen therein. In some embodiments, the first container is located within the second container. In some embodiments, the second container is configured to reduce heat transfer from the surrounding environment to the first container and the liquid hydrogen contained therein. In some embodiments, the second container is configured to evacuate (i.e., subject to low, medium, high or ultra-high vacuum conditions) or be evacuated. In some embodiments, evacuating the second container reduces convection and conduction heat transfer from the surrounding environment to the first container and the liquid hydrogen contained therein. In some embodiments, the second container is not configured to be evacuated or not evacuated. In some embodiments, the cryogenic container 510 includes one or more radiation barriers between the first container and the second container. In some embodiments, one or more radiation barriers reduce radiative heat transfer from the surrounding environment to the first container and the liquid hydrogen contained therein.

[0080] In some embodiments, the cryogenic container 510 comprises a first container, a second container, and a third container. In some embodiments, the first container is configured to contain liquid hydrogen therein. In some embodiments, the first container is located in the second container. In some embodiments, the second container is located in the third container. In some embodiments, the second container and the third container are configured to reduce heat transfer from the surrounding environment to the first container and the liquid hydrogen contained therein. In some embodiments, the second container is configured to be evacuated (i.e., subjected to low, medium, high or ultra-high vacuum conditions) or evacuated. In some embodiments, evacuating the second container reduces convection and conduction heat transfer from the surrounding environment to the first container and the liquid hydrogen contained therein. In some embodiments, the second container is not configured to be evacuated or not evacuated. In some embodiments, the cryogenic container 510 comprises one or more radiation barriers located between the first container and the second container. In some embodiments, one or more radiation barriers reduce radiative heat transfer from the surrounding environment to the first container and the liquid hydrogen contained therein. In some embodiments, the third container is configured to contain a cryogenic liquid (e.g., liquid nitrogen) therein. In some embodiments, accommodating a cryogenic liquid in the third container reduces heat transfer from the surrounding environment to the first container and the liquid hydrogen contained therein. In some embodiments, the cryogenic container 510 includes one or more radiation barriers located between the first container and the third container. In some embodiments, the one or more radiation barriers reduce radiative heat transfer from the surrounding environment to the first container and the liquid hydrogen contained therein.

[0081] In some embodiments, the cryogenic container 510 comprises a first container, a second container, a third container, and a fourth container. In some embodiments, the first container is configured to contain liquid hydrogen therein. In some embodiments, the first container is located in the second container. In some embodiments, the second container is located in the third container. In some embodiments, the third container is located in the fourth container. In some embodiments, the second container, the third container, and the fourth container are configured to reduce heat transfer from the surrounding environment to the first container and the liquid hydrogen contained therein. In some embodiments, the second container is configured to be evacuated (i.e., subjected to low, medium, high, or ultra-high vacuum conditions) or evacuated. In some embodiments, evacuating the second container reduces convection and conduction heat transfer from the surrounding environment to the first container and the liquid hydrogen contained therein. In some embodiments, the second container is not configured to be evacuated or not evacuated. In some embodiments, the cryogenic container 510 comprises one or more radiation barriers located between the first container and the second container. In some embodiments, one or more radiation barriers reduce radiative heat transfer from the surrounding environment to the first container and the liquid hydrogen contained therein. In some embodiments, the third container is configured to contain a cryogenic liquid (e.g., liquid nitrogen) therein. In some embodiments, containing cryogenic liquid in the third container reduces heat transfer from the surrounding environment to the first container and the liquid hydrogen contained therein. In some embodiments, the cryogenic container 510 includes one or more radiation barriers between the first container and the third container. In some embodiments, one or more radiation barriers reduce radiative heat transfer from the surrounding environment to the first container and the liquid hydrogen contained therein. In some embodiments, the fourth container is configured to evacuate (i.e., subject to low, medium, high or ultra-high vacuum conditions) or be evacuated. In some embodiments, evacuating the fourth container reduces convection and conduction heat transfer from the surrounding environment to the first container and the liquid hydrogen contained therein. In some embodiments, the fourth container is not configured to be evacuated or not evacuated. In some embodiments, the cryogenic container 510 includes one or more radiation barriers between the first container and the fourth container. In some embodiments, one or more radiation barriers reduce radiative heat transfer from the surrounding environment to the first container and the liquid hydrogen contained therein.

[0082] In some embodiments, the system 500A includes a chamber 520. In some embodiments, the chamber 520 is fluidly coupled to the cryogenic container 510. In some embodiments, the chamber 520 is configured to receive liquid hydrogen from the cryogenic container 510. In some embodiments, the chamber 520 is configured to boil the received liquid hydrogen to form a first hydrogen gas. In some embodiments, the chamber 520 includes a heater configured to boil the received liquid hydrogen to form a first hydrogen gas. In some embodiments, the first 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 of parahydrogen gas. In some embodiments, the first hydrogen gas includes at most 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. In some embodiments, the first hydrogen gas includes parahydrogen gas in an amount within a range defined by any two of the aforementioned values.

[0083] In some embodiments, system 500A includes 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 fluid pump ( Figure 5A In some embodiments, the gas cylinder or fluid pump is configured to deliver the first hydrogen gas to the solution. In some embodiments, the solution comprises a target molecule (also referred to herein as a target compound or a related molecule) or a precursor of the target molecule. In some embodiments, the target molecule or the precursor of the target molecule comprises a molecule used in PHIP, PHIP-SAH, SABRE or PHIPNOESYS applications. In some embodiments, the target molecule comprises any biologically relevant contrast agent described herein. In some embodiments, the solution further comprises a catalyst, such as a hydrogenation catalyst.

[0084] exist Figure 5A In the example shown, the system 500A is configured to generate a relatively high concentration of liquid parahydrogen in liquid hydrogen. In some embodiments, the system 500A is configured to generate a relatively high concentration of liquid parahydrogen when the hydrogen is in a liquid phase. For example, in some embodiments, the cryogenic vessel 510 is configured to contain a first parahydrogen conversion catalyst therein. In some embodiments, the first parahydrogen conversion catalyst is configured to convert liquid orthohydrogen contained in the liquid hydrogen into liquid parahydrogen. In this way, a relatively high concentration of liquid parahydrogen can be generated directly in the liquid hydrogen.

[0085] Figure 5BA third exemplary system 500B is depicted for providing parahydrogen gas for use in PHIP, PHIP-SAH, SABRE, or PHIPNOESYS applications in accordance with the disclosed embodiments. In the example shown, the system 500B includes a cryogenic container 510. In some embodiments, the cryogenic container 510 includes a Figure 5A Any cryogenic container as described.

[0086] In some embodiments, system 500B includes chamber 520. In some embodiments, chamber 520 includes Figure 5A Any chamber described.

[0087] exist Figure 5B In the example shown, the system 500B is configured to generate a relatively high concentration of liquid parahydrogen by first generating a relatively high concentration of gaseous parahydrogen when the hydrogen is in the gas phase, and then condensing the gaseous hydrogen. For example, in some embodiments, the system 500B optionally further comprises a gas-tight container 530. In some embodiments, the gas-tight container 530 is configured to contain a second hydrogen gas therein. In some embodiments, the gas-tight container 530 is configured to contain a second parahydrogen conversion catalyst therein. In some embodiments, the second parahydrogen conversion catalyst is configured to convert gaseous orthohydrogen in the second hydrogen gas into gaseous parahydrogen. Thus, in some embodiments, the airtight container 530 is configured to generate a third hydrogen gas therein that contains a relatively high amount of gaseous parahydrogen (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, at most 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 within a range defined by any two of the foregoing values).

[0088] In some embodiments, the system 500B further optionally includes a condenser 540. In some embodiments, the condenser 540 is fluidly coupled to the airtight container 530. In some embodiments, the condenser 540 is configured to receive the third hydrogen gas from the airtight container 530, condense the third hydrogen gas, and generate liquid hydrogen therefrom. In some embodiments, the condenser 540 is fluidly coupled to the cryogenic container 510 and is configured to deliver the liquid hydrogen to the cryogenic container 510.

[0089] In some embodiments, the first parahydrogen conversion catalyst (hereinafter referred to as Figure 5A Said) or the second secondary hydrogen conversion catalyst (hereinafter referred to as Figure 5BThe first or second parahydrogen conversion catalyst comprises a material configured to: (1) adsorb liquid or gaseous orthohydrogen, (2) separate liquid or gaseous orthohydrogen, and (3) release liquid or gaseous orthohydrogen, respectively. In some embodiments, the first or second parahydrogen conversion catalyst comprises a paramagnetic material. In some embodiments, the orthohydrogen comprises two hydrogen spins, and the first or second parahydrogen conversion catalyst destroys the symmetry between the two hydrogen spins, thereby converting the orthohydrogen into parahydrogen.

[0090] In some embodiments, the first or second para-hydrogen 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, ammonium ferric 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, hydrated manganese dioxide, hydrated iron oxide, hydrated iron oxide, or any possible combination of the foregoing materials.

[0091] Method for producing parahydrogen gas from liquid parahydrogen

[0092] Fig. 6A A second exemplary method 600A is depicted for providing parahydrogen gas for use in PHIP, PHIP-SAH, SABRE, or PHIPNOESYS NMR or MRI applications in accordance with the disclosed embodiments. Figure 5A The system 500A performs the method 600A.

[0093] At step 610, liquid hydrogen is received. In some embodiments, the liquid hydrogen comprises Figure 5A Any liquid hydrogen described. For example, 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 of liquid parahydrogen. In some embodiments, the liquid hydrogen comprises at most about 95 mol%, 90 mol%, 85 mol%, 80 mol%, 75 mol%, 70 mol%, 65 mol%, 60 mol%, 55 mol%, 50 mol% or less of liquid parahydrogen. In some embodiments, the liquid hydrogen comprises liquid parahydrogen in an amount within a range defined by any two of the foregoing values.

[0094] In some embodiments, liquid hydrogen is received as described herein Figure 5A For example, in some embodiments, the liquid hydrogen is received in a cryogenic container that contains 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. The invention relates to a volume of up to about 1,000L, 900L, 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 foregoing values.

[0095] At step 620, the liquid hydrogen is boiled. In some embodiments, the liquid hydrogen is boiled to form a first hydrogen gas. In some embodiments, the first hydrogen gas comprises Figure 5A For example, 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 para-hydrogen gas, at most about 95 mol%, 90 mol%, 85 mol%, 80 mol%, 75 mol%, 70 mol%, 65 mol%, 60 mol%, 55 mol%, 50 mol% or less para-hydrogen gas, or an amount of para-hydrogen gas within a range defined by any two of the foregoing values.

[0096] In some embodiments, method 600A further comprises converting liquid orthohydrogen into liquid parahydrogen using a first parahydrogen conversion catalyst. In some embodiments, the first parahydrogen conversion catalyst comprises Figure 5A Any of the first secondary hydrogenation catalysts described.

[0097] In some embodiments, method 600A further comprises delivering a first hydrogen gas to the solution. In some embodiments, the solution comprises Figure 5A In some embodiments, the solution comprises any of the solutions described herein. Figure 5A Any target molecule or any precursor of any target molecule. In some embodiments, the solution comprises Figure 5AIn some embodiments, the method 600A further comprises hydrogenating the PHIP, PHIP-SAH or PHIPNOESYS precursor with a first hydrogen to generate a target molecule. In some embodiments, the method 600A further comprises delivering the target molecule to a subject or sample. In some embodiments, the method 600A further comprises obtaining an NMR spectrum or MRI image of a subject sample in response to the target molecule.

[0098] Figure 6B A third exemplary method 600B is depicted for providing parahydrogen gas for use in PHIP, PHIP-SAH, SABRE, or PHIPNOESYS NMR or MRI applications in accordance with the disclosed embodiments. Figure 5B The system 500B executes the method 600B.

[0099] At step 602, a second hydrogen gas is obtained. In some embodiments, the second hydrogen gas comprises Figure 5B Any second hydrogen gas described.

[0100] At step 604, the gaseous orthohydrogen in the second hydrogen is converted into gaseous parahydrogen, thereby generating a third hydrogen gas. In some embodiments, the third hydrogen gas comprises Figure 5B For example, in some embodiments, the third 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 of gaseous parahydrogen, at most about 95 mol%, 90 mol%, 85 mol%, 80 mol%, 75 mol%, 70 mol%, 65 mol%, 60 mol%, 55 mol%, 50 mol% or less of gaseous parahydrogen, or an amount of gaseous parahydrogen within a range defined by any two of the foregoing values.

[0101] In some embodiments, method 600B further comprises converting gaseous orthohydrogen into gaseous parahydrogen using a second parahydrogen conversion catalyst. In some embodiments, the second parahydrogen conversion catalyst comprises Figure 5B Any second secondary hydrogenation catalyst described.

[0102] At step 606 , the third hydrogen gas is condensed to thereby generate liquid hydrogen.

[0103] At step 610, liquid hydrogen is received. In some embodiments, the liquid hydrogen comprises Figure 5BAny liquid hydrogen described. For example, 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 of liquid parahydrogen. In some embodiments, the liquid hydrogen comprises at most about 95 mol%, 90 mol%, 85 mol%, 80 mol%, 75 mol%, 70 mol%, 65 mol%, 60 mol%, 55 mol%, 50 mol% or less of liquid parahydrogen. In some embodiments, the liquid hydrogen comprises liquid parahydrogen in an amount within a range defined by any two of the foregoing values.

[0104] In some embodiments, liquid hydrogen is received as described herein Figure 5B For example, in some embodiments, the liquid hydrogen is received in a cryogenic container that contains 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. The invention relates to a volume of up to about 1,000L, 900L, 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 foregoing values.

[0105] At step 620, the liquid hydrogen is boiled. In some embodiments, the liquid hydrogen is boiled to form a first hydrogen gas. In some embodiments, the first hydrogen gas comprises Figure 5B For example, 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 para-hydrogen gas, at most about 95 mol%, 90 mol%, 85 mol%, 80 mol%, 75 mol%, 70 mol%, 65 mol%, 60 mol%, 55 mol%, 50 mol% or less para-hydrogen gas, or an amount of para-hydrogen gas within a range defined by any two of the foregoing values.

[0106] In some embodiments, method 600B further comprises delivering a first hydrogen gas to the solution. In some embodiments, the solution comprises Figure 5B In some embodiments, the solution comprises any of the solutions described herein. Figure 5BAny target molecule or any precursor of any target molecule. In some embodiments, the solution comprises Figure 5B In some embodiments, the method 600B further comprises hydrogenating the PHIP, PHIP-SAH or PHIPNOESYS precursor with a first hydrogen to generate a target molecule. In some embodiments, the method 600B further comprises delivering the target molecule to a subject or sample. In some embodiments, the method 600B further comprises obtaining an NMR spectrum or MRI image of a subject sample in response to the target molecule.

[0107] Figure 7 An exemplary Raman spectrum of a hydrogen mixture according to the disclosed embodiment is depicted, the hydrogen mixture containing more than 90% parahydrogen generated from liquid hydrogen. Liquid hydrogen is exposed to a parahydrogen conversion catalyst to convert liquid orthohydrogen into liquid parahydrogen. Liquid hydrogen is boiled to form gaseous hydrogen. The gaseous hydrogen is analyzed using a homemade Raman spectrometer. The Raman spectrometer uses laser excitation at approximately 532 nanometers (nm) and a laser power of 100 milliwatts (mW). The Raman peak corresponding to parahydrogen appears at approximately 542nm. The Raman peak corresponding to orthohydrogen appears at approximately 549nm and 556nm. The area under the corresponding peak is calculated to determine the concentration of parahydrogen and orthohydrogen in the hydrogen. In order to retrieve the area of ​​the peak, the peak is fitted to a Lorentz function. During the calculation, the anisotropy of the polarizability tensor is taken into account. Using this method, the hydrogen is calculated to contain 95.2% parahydrogen. Therefore, preparing liquid parahydrogen and boiling the liquid is a feasible method for producing hydrogen containing a high concentration of parahydrogen.

[0108] Biologically relevant contrast agents

[0109] The disclosed embodiments include systems and methods for producing and utilizing biologically relevant contrast agents with clinically relevant polarizations, concentrations, volumes, or purity. In some embodiments, the methods are used to prepare NMR materials (also referred to herein as "relevant molecules"). In some embodiments, the NMR materials are suitable for use in NMR or MRI operations. In some embodiments, the NMR materials increase NMR or MRI signals and signal-to-noise ratios (SNRs). In some embodiments, the NMR materials are suitable for use in solution NMR spectroscopy. In some embodiments, the NMR materials are chemical compounds. In some embodiments, the NMR materials are metabolites (e.g., molecules with biological relevance, such as amino acids, sugars, derivatives thereof, etc.), such as metabolites suitable for use in NMR metabolomics applications. In some embodiments, the NMR materials are suitable for in vitro detection of the metabolism of cell cultures or other biological tissues. In some embodiments, the NMR materials are used in NMR probes to study transient effects, where high signal enhancement due to hyperpolarization is required, such as proton exchange between water and biological molecules. In some embodiments, the NMR materials are small molecules or metabolites suitable for injection into cells, tissues, or organisms to be detected in MRI scans. In some embodiments, the NMR materials are introduced into the chamber for further analysis by NMR or MRI operations. In some embodiments, the NMR material is enriched with one or more deuterium ( 2 H) or carbon-13 ( 13 C) atoms.

[0110] In accordance with the disclosed embodiments, the NMR material may include a biologically relevant contrast agent. In some embodiments, the biologically relevant contrast agent may be suitable for NMR or MRI operation. In some embodiments, the biologically relevant contrast agent may increase the NMR or MRI signal or signal-to-noise ratio (SNR). In some embodiments, the biologically relevant contrast agent may be suitable for solution NMR spectroscopy. In some embodiments, the biologically relevant contrast agent may be a metabolite (e.g., a molecule with biological relevance, such as an amino acid, a sugar, a derivative thereof, etc.), such as a metabolite suitable for NMR metabolomics applications. In some embodiments, the biologically relevant contrast agent is used for perfusion imaging or contrast enhancement imaging in MRI scanning. In some embodiments, the biologically relevant contrast agent is suitable for in vitro detection of the metabolism of cell cultures or other biological tissues. In some embodiments, the biologically relevant contrast agent is used in an NMR probe to study transient effects, where a high signal enhancement due to hyperpolarization is required, such as proton exchange between water and biomolecules. In some embodiments, the biologically relevant contrast agent is a small molecule or metabolite suitable for injection into a cell, tissue or organism to be detected in an MRI scan. In some embodiments, a biologically relevant contrast agent is introduced into the chamber for further analysis by NMR or MRI procedures. In some embodiments, the biologically relevant contrast agent is enriched with one or more 2 H or 13 C atom.

[0111] In some embodiments, the biologically relevant contrast agent comprises pyruvate, lactate, α-ketoglutarate, bicarbonate, fumarate, urea, dehydroascorbate, glutamate, glutamine, acetate, dihydroxyacetone, acetoacetate, glucose, ascorbate, ketoacid, alanine, fructose, imidazole, nicotinamide, nitroimidazole, pyrazinamide, isoniazid, a conjugated acid of any of the foregoing, a natural and unnatural amino acid, an ester thereof, or a rich 2 H. 13 C or nitrogen-15( 15 N) version. In some embodiments, the biologically relevant contrast agent comprises pyruvate, lactate, α-ketoglutarate. In some embodiments, the biologically relevant contrast agent comprises pyruvate. In some embodiments, the biologically relevant contrast agent comprises lactate. In some embodiments, the biologically relevant contrast agent comprises α-ketoglutarate (e.g., ethyl α-ketoglutarate).

[0112] In some embodiments, the biologically relevant contrast agent comprises at least one non-hydrogen nuclear spin. In some embodiments, the non-hydrogen nuclear spin comprises at least one spin-1 / 2 atom. In some embodiments, the non-hydrogen nuclear spin comprises 13 C or 15N. In some embodiments, the biologically relevant contrast agent is at least partially isotopically labeled with a non-hydrogen nuclear spin. In some embodiments, the biologically relevant contrast agent is at least partially enriched in the non-hydrogen nuclear spin when compared to an analog of the biologically relevant contrast agent characterized by its natural abundance. In some embodiments, the biologically relevant contrast agent is enriched to 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%, 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 abundance, or within a range defined by any two of the foregoing values, to characterize the non-hydrogen nuclear spins.

[0113] In some embodiments, the non-H nuclear spin replaces an NMR-inactive (ie, spin-0) nucleus of an analog of a biologically relevant contrast agent that characterizes the non-H nuclear spin in its natural abundance (eg, 12 C or quadrupolar (i.e., spin > 1 / 2) nuclei) (e.g., nitrogen-14, 14 N) for example, characterized by its natural abundance 13 The analog of pyruvate of C can contain about 98.9% at any C* in the structure H3C-C*(=O)-C*OOH 12 C and about 1.1% 13 C. As a biologically relevant contrast agent, pyruvate can be alternatively enriched 13 C isotopes, such that one or both C* contain any of the abundances described herein. 13 C. As used herein, *C and C* describe 12 C or 13 C carbon isotope. For example, its natural abundance characterizes 15 The urea analog of N can contain about 99.6% of any N* in the structure H2N*-C(=O)-*NH2 14 N and about 0.4% 15 N. As a biologically relevant contrast agent, urea can be alternatively enriched 15 N isotopes, such that one or both N* comprises any of the abundances described herein. 15 N. As used herein, *N and N* describe14 N or 15 N is the nitrogen isotope of nitrogen.

[0114] Transport of liquid and / or gaseous parahydrogen

[0115] Parahydrogen can be generated at a first location (e.g., in a gas cylinder as described herein or in a cryogenic container as described herein) and subsequently 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, a car, a truck, or other location where parahydrogen can be generated. In some embodiments, the gas cylinder or cryogenic container is cooled to a temperature below room temperature before, during, or after transportation. For example, in some embodiments, the gas cylinder or cryogenic container is cooled to a temperature below about 200K, 190K, 180K, 170K, 160K, 150K, 140K, 130K, 120K, 110K, 100K, 90K, 80K, 70K, 60K, 50K or less, above about 50K, 60K, 70K, 80K, 90K, 100K, 110K, 120K, 130K, 140K, 150K, 160K, 170K, 180K, 190K, 200K or more, or a temperature within a range defined by any two of the foregoing values. In some embodiments, ice, dry ice, or liquid nitrogen is used to cool the gas cylinder or cryogenic container. In some embodiments, cooling the gas cylinder or cryogenic container increases the lifetime of the gaseous or liquid parahydrogen contained therein.

[0116] The generated parahydrogen can be transported to a second location in a gas cylinder or cryogenic container. The second location may be different from the first location. The gas cylinder or cryogenic container may be transported by a vehicle or a person. Transporting parahydrogen may involve moving the gas cylinder or cryogenic container within the same location, such as moving from one part of a room to another part of a room. Transporting a gas cylinder or cryogenic container may involve moving the gas cylinder or cryogenic container from a room in a building to a different room in the same building or to a nearby building. Transporting a gas cylinder or cryogenic container may involve moving the gas cylinder or cryogenic container to another part of the same city, a different city, a different state, a different province, a different territory, a different country or even a different continent. Transporting a gas cylinder or cryogenic container may involve bringing the gas cylinder or cryogenic container into the vicinity of an NMR device or an MRI device. Transporting a gas cylinder or cryogenic container may involve packaging or shipping the gas cylinder or cryogenic container in a suitable container.

[0117] precipitation

[0118] In various embodiments, the molecules of interest may be crystallized or precipitated from the solutions described herein. The disclosed embodiments are not limited to any particular method for inducing such precipitation. For example, such precipitation may be induced by: changing temperature or pH, applying electromagnetic stimulation (e.g., optical radiation, such as ultraviolet radiation or another optical radiation of one or more suitable wavelengths), mechanical stimulation (e.g., ultrasound, stirring or another suitable mechanical stimulation), adding another solute or solvent to the solution, or another suitable method or any combination thereof. In some embodiments, after precipitation, the molecules of interest may be separated from the solution (e.g., using a filter or another suitable method). In some embodiments, the molecules of interest may then be combined or redissolved in another solution. The solution may have properties (e.g., biocompatibility, concentration, volume, temperature, pH, polarity or other relevant properties, or any combination thereof) that are expected for NMR or MRI applications.

[0119] Use of related molecules

[0120] In some embodiments, at least a portion of the molecules of interest may be injected into a subject or patient for MRI experiments. In various embodiments, at least a portion of the molecules of interest may be used for NMR spectroscopy. At least one NMR or MRI pulse sequence may be applied to the molecules of interest.

[0121] The foregoing description is presented for illustrative purposes. It is not exhaustive and is not limited to the precise form 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, the described embodiments include hardware, but systems and methods consistent with the present disclosure may be implemented with hardware and software. In addition, although certain components have been described as being coupled to each other, such components may be integrated with each other or distributed in any suitable manner.

[0122] In addition, although illustrative embodiments have been described herein, the scope includes any and all embodiments having equivalent elements, modifications, omissions, combinations (e.g., combinations of aspects of the various embodiments), adaptations, or variations based on the present disclosure. The elements in the claims are to be interpreted broadly based on the language employed in the claims, and are not limited to the examples described in this specification or during the practice of the application, which examples are to be understood as non-exclusive. Further, the steps of the disclosed methods may be modified in any manner, including reordering steps or inserting or deleting steps.

[0123] According to the detailed description, the features and advantages of the present disclosure are obvious, 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, unless the use of plural terms is clear in a given context, it does not necessarily represent a plural number. In addition, since various modifications and changes will be easily made by studying the present disclosure, it is not desired to limit the present disclosure to the exact construction and operation shown and described, and therefore all suitable modifications and equivalents can be attributed to and fall within the scope of the present disclosure.

[0124] As used herein, unless otherwise specifically stated, the term "or" encompasses all possible combinations (both conjoint and disjoint) unless impractical. For example, if a statement is made that a component may include A or B, then unless otherwise specifically stated or impractical, the component may include A alone, or B alone, or A and B. As a second example, if a statement is made that a component may include A, B, or C, then unless otherwise specifically stated or impractical, the component may include A alone, or B alone, or C alone, or A and B, or A and C, or B and C, or A and B and C.

[0125] Description of Embodiments

[0126] Embodiment 1. A system comprising:

[0127] a gas cylinder configured to contain therein hydrogen gas comprising parahydrogen gas at a first concentration of at least 45% and a pressure of at most 40 bar;

[0128] wherein the parahydrogen gas has a decay time constant of at least 30 days; and

[0129] The parahydrogen gas is used in 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) procedures.

[0130] Embodiment 2. The system of embodiment 1, wherein the first concentration is at least 95%.

[0131] Embodiment 3. The system of embodiment 1 or 2, wherein the pressure is at most 12 bar, and wherein the decay time constant is at least 30 days.

[0132] Embodiment 4. The system of any one of embodiments 1 to 3, wherein the pressure is at most 3 bar, and wherein the decay time constant is at least 100 days.

[0133] Embodiment 5. The system of any one of embodiments 1 to 4, wherein the gas cylinder has been purged using at least one purge operation to contain the hydrogen gas therein.

[0134] Embodiment 6. The system of Embodiment 5, wherein the at least one purge operation comprises at least one member selected from the group consisting of: at least one evacuation operation, at least one heating operation, and at least one filling operation.

[0135] Embodiment 7. The system of any one of embodiments 1 to 6, further comprising a first flow system fluidly coupled to the gas cylinder and the mixing chamber;

[0136] wherein the first flow system is configured to direct the parahydrogen gas to the mixing chamber;

[0137] wherein the mixing chamber is configured to contain a first solution therein,

[0138] wherein the first solution contains a related molecule or a derivative of the related molecule;

[0139] wherein said related molecule is used in said NMR or MRI procedure; and

[0140] wherein the mixing chamber is configured to mix the parahydrogen gas with the related molecule or the derivative of the related molecule.

[0141] Embodiment 8. The system of embodiment 7, wherein the mixing chamber is configured to mix the parahydrogen gas with the molecules of interest in the presence of a polarization transfer catalyst, thereby transferring spin order from the parahydrogen gas to the molecules of interest via a SABRE interaction.

[0142] Embodiment 9. A system according to embodiment 7, wherein the derivative of the related molecule contains at least one double bond or triple bond, and wherein the mixing chamber is configured to mix the parahydrogen gas with the derivative of the related molecule in the presence of a hydrogenation catalyst, thereby inducing a parahydrogenation reaction between the parahydrogen gas and the derivative of the related molecule, thereby hydrogenating the at least one double bond or triple bond and forming the related molecule, and transferring the spin order from the parahydrogen gas to the related molecule via a PHIP interaction.

[0143] Embodiment 10. A system according to embodiment 7, wherein the derivative of the related molecule contains at least one double bond or triple bond, and wherein the mixing chamber is configured to mix the parahydrogen gas with the derivative of the related molecule in the presence of a hydrogenation catalyst, thereby inducing a parahydrogenation reaction between the parahydrogen gas and the derivative of the related molecule, thereby hydrogenating the at least one double bond or triple bond and forming a parahydrogenated derivative of the related molecule.

[0144] Embodiment 11. The system of embodiment 9, further comprising a second flow system configured to be fluidly coupled to the mixing chamber and the hydrolysis chamber;

[0145] wherein the second flow system is configured to direct the first solution containing the para-hydrogenated derivative of the molecule of interest to the hydrolysis chamber;

[0146] wherein said hydrolysis chamber is configured to contain said first solution containing said para-hydrogenated derivative of said molecule of interest;

[0147] wherein the hydrolysis chamber is configured to mix the first solution containing the secondary hydrogenated derivative of the related molecule with a hydrolyzing agent, thereby hydrolyzing the secondary hydrogenated derivative of the related molecule to form a hydrolyzed sidearm and the related molecule via PHIP-SAH interaction.

[0148] Embodiment 12. The system according to any one of embodiments 7 to 11, further comprising a third flow system, the third flow system being fluidly coupled to the mixing chamber or the hydrolysis chamber and the purification chamber;

[0149] The third flow system is configured to direct the first solution containing the molecule of interest to the purification chamber.

[0150] Embodiment 13. A system according to embodiment 12, wherein the purification chamber is configured to mix the first solution containing the related molecules with a second solution to form a third solution containing the related molecules, and the third solution contains a reduced concentration of contaminants compared to the first solution.

[0151] Embodiment 14. A system according to embodiment 13, wherein the purification chamber is configured to perform a precipitation reaction on the first solution containing the related molecules to form a precipitate of the related molecules, and mix the precipitate of the related molecules with a second solution to form a third solution containing the related molecules, wherein the third solution contains a reduced concentration of contaminants compared to the first solution.

[0152] Embodiment 15. A system according to any one of embodiments 7 to 14, wherein the relevant molecules comprise a biologically relevant contrast agent selected from the group consisting of: pyruvate, glutamate, glutamine, lactate, acetate, acetoacetate, ketoate, alanine, fructose, fumarate, bicarbonate, urea, dehydroascorbate, α-ketoglutarate, dihydroxyacetone, glucose, ascorbate and conjugated acids thereof.

[0153] Embodiment 16. A method comprising:

[0154] containing hydrogen gas in the gas cylinder, the hydrogen gas comprising parahydrogen gas at a first concentration of at least 45% and a pressure of at most 40 bar;

[0155] wherein the parahydrogen gas has a decay time constant of at least 30 days; and

[0156] The parahydrogen gas is used in 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) procedures.

[0157] Embodiment 17. The method of embodiment 16, wherein the first concentration is at least 95%.

[0158] Embodiment 18. The method of embodiment 16 or 17, wherein the pressure is at most 12 bar, and wherein the decay time constant is at least 30 days.

[0159] Embodiment 19. The method of any one of embodiments 16 to 18, wherein the pressure is at most 3 bar, and wherein the decay time constant is at least 100 days.

[0160] Embodiment 20. The method of any one of Embodiments 16 to 19, wherein the gas cylinder has been purged using at least one purge operation to contain the hydrogen gas therein.

[0161] Embodiment 21. The method of Embodiment 20, wherein the at least one purge operation comprises at least one member selected from the group consisting of: at least one evacuation operation, at least one heating operation, and at least one filling operation.

[0162] Embodiment 22. The method according to any one of embodiments 16 to 21, further comprising mixing the parahydrogen gas with the first solution;

[0163] wherein the first solution contains a related molecule or a derivative of the related molecule; and

[0164] wherein said related molecule is used in said NMR or MRI procedure; and

[0165] Embodiment 23. The method according to embodiment 22 further comprises mixing the parahydrogen gas with the related molecules in the presence of a polarization transfer catalyst, thereby transferring the spin order from the parahydrogen gas to the related molecules via SABRE interaction.

[0166] Embodiment 24. The method according to embodiment 22 further comprises mixing the parahydrogen gas with the derivative of the related molecule in the presence of a hydrogenation catalyst, thereby inducing a parahydrogenation reaction between the parahydrogen gas and the derivative of the related molecule, thereby hydrogenating at least one double bond or triple bond of the derivative of the related molecule and forming the related molecule, and transferring the spin order from the parahydrogen gas to the related molecule via PHIP interaction.

[0167] Embodiment 25. The method according to embodiment 22 further comprises mixing the parahydrogen gas with the derivative of the related molecule in the presence of a hydrogenation catalyst, thereby inducing a parahydrogenation reaction between the parahydrogen gas and the derivative of the related molecule, thereby hydrogenating at least one double bond or triple bond of the derivative of the related molecule and forming a parahydrogenated derivative of the related molecule.

[0168] Embodiment 26. The method according to embodiment 25 further comprises mixing the first solution containing the secondary hydrogenated derivative of the related molecule with a hydrolyzing agent, thereby hydrolyzing the secondary hydrogenated derivative of the related biological molecule, thereby forming a hydrolyzed side arm and the related molecule via PHIP-SAH interaction.

[0169] Embodiment 27. The method according to any one of embodiments 22 to 26, further comprising purifying the first solution containing the related molecules.

[0170] Embodiment 28. A method according to embodiment 27, wherein purifying the first solution containing the related molecules comprises mixing the first solution containing the related molecules with a second solution to form a third solution containing the related molecules, and the third solution contains a reduced concentration of contaminants compared to the first solution.

[0171] Embodiment 29. A method according to embodiment 27, wherein purifying the first solution containing the related molecules comprises performing a precipitation reaction on the first solution containing the related molecules to form a precipitate of the related molecules, and mixing the precipitate of the related molecules with a second solution to form a third solution containing the related molecules, wherein the third solution contains a reduced concentration of contaminants compared to the first solution.

[0172] Embodiment 30. A method according to any one of embodiments 22 to 29, wherein the relevant molecule comprises a biologically relevant contrast agent selected from the group consisting of: pyruvate, glutamate, glutamine, lactate, acetate, acetoacetate, ketoate, alanine, fructose, fumarate, bicarbonate, urea, dehydroascorbate, α-ketoglutarate, dihydroxyacetone, glucose, ascorbate and their conjugated acids.

[0173] Embodiment 31. A system comprising:

[0174] a cryogenic container configured to contain liquid hydrogen therein; and

[0175] a chamber fluidly coupled to the cryogenic vessel, the chamber configured to receive the liquid hydrogen from the cryogenic vessel and boil the received liquid hydrogen to form a first hydrogen gas comprising at least 50, 55, 60, 65, 70, 75, 80, 85, 90, or 95 mole percent parahydrogen gas.

[0176] Embodiment 32. The system of Embodiment 31, further comprising a port fluidly coupled to the chamber, the port being configured to fluidly couple the chamber to a gas cylinder or a fluid pump.

[0177] Embodiment 33. A system according to embodiment 32, wherein the gas cylinder or the fluid pump is configured to deliver the first hydrogen gas to a solution comprising a precursor of a target molecule and a catalyst, thereby hydrogenating the precursor in the presence of the catalyst and thereby forming the target molecule.

[0178] Embodiment 34. The system of embodiment 33, wherein the precursor comprises a parahydrogen induced polarization (PHIP) precursor or a PHIP-sidearm hydrogenation (PHIP-SAH) precursor.

[0179] Embodiment 35. The system of any one of Embodiments 31 to 34, wherein the chamber comprises a heater configured to boil the received liquid hydrogen.

[0180] Embodiment 36. The system of any one of Embodiments 31 to 35, wherein the liquid hydrogen comprises at least 50, 55, 60, 65, 70, 75, 80, 85, 90, or 95 mole percent liquid parahydrogen.

[0181] Embodiment 37. A system according to any one of embodiments 31 to 36, wherein the cryogenic container is further configured to contain a first para-hydrogen conversion catalyst therein, wherein the first para-hydrogen conversion catalyst is configured to convert liquid orthohydrogen into liquid parahydrogen.

[0182] Embodiment 38. The system according to any one of embodiments 31 to 36, further comprising:

[0183] a gas-tight container configured to contain a second hydrogen gas therein and convert gaseous orthohydrogen in the second hydrogen gas into gaseous parahydrogen, thereby generating a third hydrogen gas, the third hydrogen gas comprising at least 50, 55, 60, 65, 70, 75, 80, 85, 90, or 95 mole percent gaseous parahydrogen; and

[0184] A condenser is configured to receive the third hydrogen gas and generate the liquid hydrogen therefrom, wherein the condenser is fluidly coupled to the cryogenic container and configured to deliver the liquid hydrogen to the cryogenic container.

[0185] Embodiment 39. A system according to embodiment 38, wherein the airtight container is further configured to accommodate a second para-hydrogen conversion catalyst therein, wherein the second para-hydrogen conversion catalyst is configured to convert the gaseous ortho-hydrogen into the gaseous para-hydrogen.

[0186] Embodiment 40. A system according to embodiment 37 or 39, wherein the first para-hydrogen conversion catalyst or the second para-hydrogen conversion catalyst comprises a material configured to adsorb the liquid orthohydrogen or the gaseous orthohydrogen, separate the liquid orthohydrogen or the gaseous orthohydrogen, and release the liquid orthohydrogen or the gaseous orthohydrogen.

[0187] Embodiment 41. A system according to embodiment 37 or 39, wherein the liquid orthohydrogen or the gaseous orthohydrogen comprises two hydrogen spins, and wherein the first parahydrogen conversion catalyst or the second parahydrogen conversion catalyst comprises a paramagnetic material, and the paramagnetic material is configured to destroy the symmetry between the two hydrogen spins, thereby converting the liquid orthohydrogen or the gaseous orthohydrogen into the liquid parahydrogen or the gaseous parahydrogen.

[0188] Embodiment 42. A system according to embodiments 37, 39, 40 or 41, wherein the first parahydrogen conversion catalyst or the 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, hydrated manganese dioxide, hydrated iron oxide, and hydrated iron oxide.

[0189] Embodiment 43. A method comprising:

[0190] receiving liquid hydrogen; and

[0191] The liquid hydrogen is boiled to form a first hydrogen gas comprising at least 50, 55, 60, 65, 70, 75, 80, 85, 90, or 95 mole percent parahydrogen gas.

[0192] Embodiment 44. The method of embodiment 43, further comprising delivering the first hydrogen gas to a solution comprising a precursor of a target molecule and a catalyst.

[0193] Embodiment 45. The method according to embodiment 44 further comprises using the first hydrogen gas to hydrogenate the precursor in the presence of the catalyst to form the target molecule.

[0194] Embodiment 46. The method of embodiment 45, wherein the precursor comprises a parahydrogen induced polarization (PHIP) precursor or a PHIP-sidearm hydrogenation (PHIP-SAH) precursor.

[0195] Embodiment 47. The method according to any one of Embodiments 44 to 46 further comprises delivering the target molecule to a subject or a sample, and obtaining a nuclear magnetic resonance (NMR) spectrum or a magnetic resonance imaging (MRI) image of the subject or the sample in response to the target molecule.

[0196] Embodiment 48. The method according to any one of embodiments 43 to 47 further comprises using a first para-hydrogen conversion catalyst, wherein the first para-hydrogen conversion catalyst is configured to convert liquid orthohydrogen into liquid parahydrogen.

[0197] Embodiment 49. The method according to any one of embodiments 43 to 47, further comprising:

[0198] Obtaining a second hydrogen gas;

[0199] converting gaseous orthohydrogen in the second hydrogen gas into gaseous parahydrogen to produce a third hydrogen gas comprising at least 50, 55, 60, 65, 70, 75, 80, 85, 90, or 95 mole percent gaseous parahydrogen; and

[0200] The third hydrogen gas is condensed to generate the liquid hydrogen from the third hydrogen gas.

[0201] Embodiment 50. The method according to embodiment 49 further comprises converting the gaseous orthohydrogen into the gaseous parahydrogen using a second parahydrogen conversion catalyst.

[0202] Embodiment 51. A method according to embodiment 48 or 50, wherein the first para-hydrogen conversion catalyst or the second para-hydrogen conversion catalyst comprises a material configured to adsorb the liquid orthohydrogen or the gaseous orthohydrogen, separate the liquid orthohydrogen or the gaseous orthohydrogen, and release the liquid orthohydrogen or the gaseous orthohydrogen.

[0203] Embodiment 52. A method according to embodiment 48 or 50, wherein the liquid orthohydrogen or the gaseous orthohydrogen comprises two hydrogen spins, and wherein the first parahydrogen conversion catalyst or the second parahydrogen conversion catalyst comprises a paramagnetic material, and the paramagnetic material is configured to destroy the symmetry between the two hydrogen spins, thereby converting the liquid orthohydrogen or the gaseous orthohydrogen into the liquid parahydrogen or the gaseous parahydrogen.

[0204] Embodiment 53. The method of claim 48, 50, 51 or 52, wherein the first parahydrogenation catalyst or the second parahydrogenation 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, hydrated manganese dioxide, hydrated iron oxide, and hydrated iron oxide.

Claims

1. A system comprising: a gas cylinder configured to contain therein hydrogen gas comprising parahydrogen gas at a first concentration of at least 45% and a pressure of at most 40 bar; wherein the parahydrogen gas has a decay time constant of at least 30 days; and The parahydrogen gas is used in 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) procedures.

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

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

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

5. The system of claim 1, wherein the gas cylinder has been purged using at least one purge operation to contain the hydrogen gas therein.

6. The system of claim 5, wherein the at least one purge operation comprises at least one member selected from the group consisting of: at least one evacuation operation, at least one heating operation, and at least one filling operation.

7. The system of claim 1, further comprising a first flow system fluidly coupled to the gas cylinder and the mixing chamber; wherein the first flow system is configured to direct the parahydrogen gas to the mixing chamber; wherein the mixing chamber is configured to contain a first solution therein, wherein the first solution contains a related molecule or a derivative of the related molecule; wherein said related molecule is used in said NMR or MRI procedure; and wherein the mixing chamber is configured to mix the parahydrogen gas with the related molecule or the derivative of the related molecule.

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

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

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

11. The system of claim 9, further comprising a second flow system configured to be fluidly coupled to the mixing chamber and the hydrolysis chamber; wherein the second flow system is configured to direct the first solution containing the para-hydrogenated derivative of the molecule of interest to the hydrolysis chamber; wherein said hydrolysis chamber is configured to contain said first solution containing said para-hydrogenated derivative of said molecule of interest; wherein the hydrolysis chamber is configured to mix the first solution containing the secondary hydrogenated derivative of the related molecule with a hydrolyzing agent, thereby hydrolyzing the secondary hydrogenated derivative of the related molecule to form a hydrolyzed sidearm and the related molecule via PHIP-SAH interaction.

12. The system of claim 7, further comprising a third flow system fluidly coupled to the mixing chamber or the hydrolysis chamber and purification chamber; The third flow system is configured to direct the first solution containing the molecule of interest to the purification chamber.

13. The system of claim 12, wherein the purification chamber is configured to mix the first solution containing the molecules of interest with a second solution to form a third solution containing the molecules of interest, the third solution comprising a reduced concentration of contaminants compared to the first solution.

14. A system according to claim 13, wherein the purification chamber is configured to perform a precipitation reaction on the first solution containing the related molecules to form a precipitate of the related molecules, and mix the precipitate of the related molecules with a second solution to form a third solution containing the related molecules, wherein the third solution contains a reduced concentration of contaminants compared to the first solution.

15. A system comprising: a cryogenic container configured to contain liquid hydrogen therein; and a chamber fluidly coupled to the cryogenic vessel, the chamber configured to receive the liquid hydrogen from the cryogenic vessel and boil the received liquid hydrogen to form a first hydrogen gas comprising at least 50, 55, 60, 65, 70, 75, 80, 85, 90, or 95 mole percent parahydrogen gas.

16. The system of claim 15, further comprising a port fluidly coupled to the chamber, the port configured to fluidly couple the chamber to a gas cylinder or a fluid pump.

17. The system of claim 16, wherein the gas cylinder or the fluid pump is configured to deliver the first hydrogen gas to a solution comprising a precursor of a target molecule and a catalyst, thereby hydrogenating the precursor in the presence of the catalyst and thereby forming the target molecule.

18. The system of claim 17, wherein the precursor comprises a parahydrogen induced polarization (PHIP) precursor or a PHIP-sidearm hydrogenation (PHIP-SAH) precursor.

19. The system of claim 15, wherein the chamber comprises a heater configured to boil the received liquid hydrogen.

20. The system of claim 15, wherein the liquid hydrogen comprises at least 50, 55, 60, 65, 70, 75, 80, 85, 90, or 95 mole percent liquid parahydrogen.

21. The system of claim 15, wherein the cryogenic vessel is further configured to contain a first para-hydrogen conversion catalyst therein, wherein the first para-hydrogen conversion catalyst is configured to convert liquid ortho-hydrogen into liquid para-hydrogen.

22. The system of claim 15, further comprising: a gas-tight container configured to contain a second hydrogen gas therein and convert gaseous orthohydrogen in the second hydrogen gas into gaseous parahydrogen, thereby generating a third hydrogen gas, the third hydrogen gas comprising at least 50, 55, 60, 65, 70, 75, 80, 85, 90, or 95 mole percent gaseous parahydrogen; and A condenser is configured to receive the third hydrogen gas and generate the liquid hydrogen therefrom, wherein the condenser is fluidly coupled to the cryogenic container and configured to deliver the liquid hydrogen to the cryogenic container.

23. The system of claim 22, wherein the airtight container is further configured to contain a second para-hydrogen conversion catalyst therein, wherein the second para-hydrogen conversion catalyst is configured to convert the gaseous ortho-hydrogen into the gaseous para-hydrogen.

24. The system of claim 21 or 23, wherein the first para-hydrogen conversion catalyst or the second para-hydrogen conversion catalyst comprises a material configured to adsorb the liquid ortho-hydrogen or the gaseous ortho-hydrogen, separate the liquid ortho-hydrogen or the gaseous ortho-hydrogen, and release the liquid ortho-hydrogen or the gaseous ortho-hydrogen.

25. The system of claim 21 or 23, wherein the liquid orthohydrogen or the gaseous orthohydrogen comprises two hydrogen spins, and wherein the first parahydrogen conversion catalyst or the second parahydrogen conversion catalyst comprises a paramagnetic material configured to break the symmetry between the two hydrogen spins, thereby converting the liquid orthohydrogen or the gaseous orthohydrogen into the liquid parahydrogen or the gaseous parahydrogen.

26. The system of claim 21 or 23, wherein the first parahydrogenation catalyst or the second parahydrogenation 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, hydrated manganese dioxide, hydrated iron oxide, and hydrated iron oxide.

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