The present invention generally pertains to methods of characterizing antibody higher order structure. In particular, the present invention pertains to the use of novel NMR methods to compare manufacturing process variability in antibody higher order structure.

The present invention relates to a separation method comprising: i) providing an aqueous solution comprising a target compound; ii) applying a separation step to the aqueous solution, thereby providing a plurality of fractions of the aqueous solution: iii) determining a concentration parameter indicating a concentration of the target compound in at least part of the fractions; iv) determining a nuclear magnetic resonance (NMR) parameter by applying an NMR measurement to the fractions, the NMR parameter indicating a nuclear magnetic spin relaxation in said at least part of the fractions; and v) determining a target parameter of said at least part of the fractions based on the concentration parameter and the nuclear magnetic resonance parameter. The present invention further relates to separation systems, uses, preparations, and methods related thereto.

The current invention is based, at least in part, on the finding that the transverse nuclear magnetic spin relaxation time T2 and the transverse nuclear magnetic spin relaxation rate R2, respectively, of protons of water molecules in an aqueous solution comprising viral particles depends on the loading status (full vs. empty) of the viral particle. Thus, one aspect of the current invention is a method for determining the ratio of loaded viral particles to empty viral particles in a sample, comprising the steps of determining a nuclear magnetic resonance (NMR) parameter related to the protons of the water molecules present in an aqueous solution comprising a mixture of loaded and empty viral particles by applying an NMR measurement to the solution, and determining the ratio of loaded viral particles to empty viral particles with the NMR parameter determined in the previous step based on a calibration function.

A method of determining patient responsiveness to a drug by the use of spectroscopy to obtain patient metabolite data and relating that data to data obtained from a statistically significant group of patients taking the same drug in order to obtain a result indicating responsiveness of a particular patient to treatment with a particular drug.

The present invention discloses a method of species identification and quality detection of liquid-like samples based on nuclear magnetic resonance technology. In this invention, a two-dimensional relaxation signal containing the .sup.1H T.sub.1 and T.sub.2 relaxation properties of liquid-like samples is obtained by applying a specially designed composite pulse sequence to liquid-like samples, and a fingerprint spectrum from this signal is established. The fingerprint spectrum can be associated with the essential characteristics of the tested sample, thus can be used to distinguish a specific liquid-like sample from the others. The fingerprint spectrum can be easily converted into a digital form, which is not only suitable for constructing big data of fingerprint spectrum for liquid-like samples, but also can be used for quality detection and authenticity judgment of liquid-like samples based on artificial intelligence. The present invention has the advantages of no need for sample pretreatment, non-destructive sample testing, convenience, quickness, excellent operability, good stability and reproducibility, etc., which can be used for species identification and quality detection of a variety of liquid-like samples, which has a wide application value.

Disclosed herein are methods for imaging a tissue in a subject that involves administering to the subject a composition comprising deuterium-labeled glycolytic or fatty acid substrate and imaging the subject with deuterium magnetic resonance imaging (DMI) to detect hydrogen-deuterium oxide (HDO) in tissues of the subject. The disclosed methods can be used to detect changes in metabolic activity in a tissue. The disclosed methods can also be used to detect cancers.

The present disclosure provides methods for measuring interactions between a ligand and a protein, comprising hyperpolarizing a ligand in a solvent using para-hydrogen to form a first solution; transferring the first solution to a detector; mixing the first solution with a protein solution, the protein solution having one or more ligands of interest therein; and determining interactions of the hyperpolarized ligand with the one or more ligands of interest by observing a change in an NMR signal of the hyperpolarized ligand. The ligand can include one or more sites for hyperpolarization by parahydrogen, and one or more binding sites for interaction with the protein.

The present disclosure provides methods for measuring interactions between a ligand and a protein, comprising hyperpolarizing a ligand in a solvent using para-hydrogen to form a first solution; transferring the first solution to a detector; mixing the first solution with a protein solution, the protein solution having one or more ligands of interest therein; and determining interactions of the hyperpolarized ligand with the one or more ligands of interest by observing a change in an NMR signal of the hyperpolarized ligand. The ligand can include one or more sites for hyperpolarization by parahydrogen, and one or more binding sites for interaction with the protein.

Phase-incrementing MRSI (pi-MRSI) method has resolved overlapping biomarker images in the presence of a read-gradient. On a Bruker 9.4T MRI spectrometer, the pi-SEE-HSelMQC sequence was implemented. The choline-selective and lactate CH-selective RF pulses were phase incremented by 10° in opposite signs, synchronized with the phase-encoding steps. The lactate and choline images from a yogurt phantom displayed opposite image offsets without image overlapping. In vivo one-dimensional pi-SEE-HSelMQC CSI images of lactate and choline, acquired from the MDA-MB-231 human breast cancer xenograft in a nude mouse, as well as two-dimensional pi-SEE-HSelMQC imaging of lactate and choline acquired from the PC3 human prostate cancer xenograft in a nude mouse, also had opposite image offsets, shifted away from the spurious residual water signals in the image center. The pi-SEE-HSelMQC method completely suppresses lipid and water with potential clinical applications in disease diagnosis and therapeutic interventions.

A system and method for determining a nuclear magnetic resonance relaxation time of a probe includes polarizing first nuclei and second nuclei by applying a longitudinal static magnetic field to the probe, exchanging the polarizations of the first nuclei and the second nuclei by irradiating a swap sequence of transverse magnetic field pulses, transversely magnetizing the second nuclei by irradiating at least one excitation pulse and measuring the resulting magnetization signal of the second nuclei, and determining the nuclear magnetic resonance relaxation time of the second nuclei based on the measured magnetization signal of the second nuclei.