Magnetic levitation techniques to separate and analyze molecular entities

Patent metadata

Field	Value
Publication number	US-11548011-B2
Application number	US-201917262644-A
Country	US
Kind code	B2
Filing date	Jul 23, 2019
Priority date	Jul 23, 2018
Publication date	Jan 10, 2023
Grant date	Jan 10, 2023

Abstract

The disclosure describes systems and methods for separating a plurality of molecular entities with differing densities. The system includes: a pair of magnetic poles of like polarity to provide a magnetic field; and a container holding the plurality of molecular entities in a fluid medium comprising nanoparticles that substantially change a magnetic susceptibility of the fluid medium such that, when the container is placed inside the magnetic field, sufficient gradients in an effective density of the fluid medium are generated inside the container to levitate the plurality of molecular entities to respective layers within the container, each respective layer corresponding to a respective density.

First claim

What is claimed is:

1. A system for separating a plurality of sub-micron sized plasma molecular entities with differing densities, the system comprising:
a pair of magnetic poles of like polarity to provide a magnetic field; and
a container holding the plurality of sub-micron sized plasma molecular entities in a fluid medium comprising superparamagnetic nanoparticles that substantially change a magnetic susceptibility of the fluid medium while preserving a stability of the sub-micron sized plasma molecular entities such that, when the container is placed inside the magnetic field, sufficient gradients in an effective density of the fluid medium are generated inside the container to levitate the plurality of sub-micron sized plasma molecular entities, with the preserved stability, to respective layers within the container, each respective layer corresponding to a respective density.

2. The system of claim 1 , wherein the superparamagnetic nanoparticles comprise at least one of: superparamagnetic iron oxide nanoparticles (SPIO), monocrystalline iron oxide nanoparticles (MIONs), Ultrasmall Superparamagnetic Iron Oxides (USPIOs), or a type of ferromagnetic or ferrimagnetic nanoparticles.

3. The system of claim 2 , wherein the type of ferromagnetic or ferrimagnetic nanoparticles include at least one of: a yttrium iron garnet, a cubic ferrite; and a hexagonal ferrite.

4. The system of claim 1 , wherein the fluid medium includes at least one of: a superparamagnetic nanoparticle ferrofluid, a ferromagnetic nanoparticle ferrofluid, or a ferrimagnetic nanoparticle ferrofluid.

5. The system of claim 1 , wherein the superparamagnetic nanoparticles are not attached or bound to at least portions of the plurality of sub-micron sized plasma molecular entities.

6. The system of claim 1 , wherein the superparamagnetic nanoparticles are attached or bound to at least portions of the plurality of sub-micron sized plasma molecular entities.

7. The system of claim 1 , wherein a concentration of the superparamagnetic nanoparticles in the fluid medium is about 0.001 mg/ml to about 30 mg/ml.

8. The system of claim 1 , wherein the pair of magnetic poles are separated by a distance accommodating the container, wherein the distance is about 0.005 cm to 50 cm, and wherein the magnetic field is about 0.002 Tesla to 10 Tesla.

9. The system of claim 1 , wherein the container comprises a port to allow extraction of at least portions of a respective layer of the plurality of sub-micron sized plasma molecular entities from the container.

10. The system of claim 1 , further comprising an imaging system comprising one or more camera devices configured to perform image-based detection of the plurality of sub-micron sized plasma molecular entities levitated to the respective layers within the container.

11. The system of claim 1 , further comprising a laser system that includes:
a laser source configured to generate a laser beam;
passive optical components configured to guide the laser beam to irradiate the container; and
one or more detectors configured to record an optical signal from the respective layers in response to being irradiated by the laser beam,
wherein the laser source includes a laser diode configured to output an optical power between 1 mW and 30 mW with an optical wavelength between 400 nm and 1300 nm,
wherein the passive optical components include at least one of: a beam expander, an aperture, a grating, or a fiber, and
wherein the one or more detectors include at least one charge-coupled device (CCD).

12. A method for separating a plurality of sub-micron sized plasma molecular entities with differing densities, the method comprising:
introducing the plurality of sub-micron sized plasma molecular entities into a fluid medium comprising superparamagnetic nanoparticles that substantially change a magnetic susceptibility of the fluid medium while preserving a stability of the sub-micron sized plasma molecular entities; and
subsequently placing the fluid medium in a magnetic field to generate sufficient gradients in an effective density of the fluid medium inside a container such that the plurality of sub-micron sized plasma molecular entities, with the preserved stability, are levitated to respective layers inside the container, each respective layer corresponding to a respective density.

13. The method of claim 12 , further comprising:
extracting at least a portion of a respective layer comprising at least one of the plurality of sub-micron sized plasma molecular entities; and
analyzing the portion of the respective layer using a technique for proteomics, lipidomics, or metabolomics, wherein the technique for proteomics, lipidomics, or metabolomics comprises at least one of: a liquid chromatography mass spectroscopy (LC-MS/MS) technique, or a gel-electrophoresis technique.

14. The method of claim 12 , further comprising:
adjusting a concentration of the superparamagnetic nanoparticles in the fluid medium to change a separation of the respective layers, wherein the concentration vary from about 0.001 mg/ml to about 30 mg/ml, wherein the nanoparticles comprise at least one of: superparamagnetic iron oxide nanoparticles (SPIO), Ultrasmall Superparamagnetic Iron Oxides (USPIOs), or a type of ferromagnetic or ferrimagnetic nanoparticles,
wherein the type of ferromagnetic or ferrimagnetic nanoparticles includes at least one of: a yttrium iron garnet, a cubic ferrite, and a hexagonal ferrite, and
wherein the fluid medium includes at least one of: a superparamagnetic nanoparticle ferrofluid, a ferromagnetic nanoparticle ferrofluid, or a ferrimagnetic nanoparticle ferrofluid.

15. The method of claim 14 , wherein the superparamagnetic nanoparticles are not attached to at least portions of the plurality of sub-micron sized plasma molecular entities.

16. The method of claim 14 , wherein the superparamagnetic nanoparticles are attached or bound to at least portions of the plurality of sub-micron sized plasma molecular entities.

17. The method of claim 12 , further comprising:
optically resolving the respective layers of the plurality of sub-micron sized plasma molecular entities to perform image-based detection of the plurality of sub-micron sized plasma molecular entities levitated to the respective layers.

18. The method of claim 17 , wherein placing the fluid medium in the magnetic field occurs at a first time point, wherein optically resolving the respective layers of the plurality of sub-micron sized plasma molecular entities occurs at a second time point, and wherein the first time point precedes the second time point by about 10 seconds to 10 hours.

19. The method of claim 17 , wherein optically resolving comprises:
energizing a laser source to generate a laser beam;
irradiating each of the respective layers with the laser beam; and
recording an optical signal from each of the respective layers in response to being irradiated by the laser beam, wherein the laser beam is characterized as having an optical power between 1 mW and 30 mW and an optical wavelength between 400 nm and 1300 nm.

20. The method of claim 12 , wherein the magnetic field is characterized as having a field strength of about 0.002 Tesla to 10 Tesla.

Assignees

• Brigham & Womens Hospital Inc

Inventors

• Mahmoudi Morteza

Classifications

• G01N33/54346

  Nanoparticles · CPC title

• B03C2201/26

  for use in medical or biological applications · CPC title

• B03C1/0335

  using coils · CPC title

• B03C1/32 Primary

  acting on the medium containing the substance being separated, e.g. magneto-gravimetric-, magnetohydrostatic-, or magnetohydrodynamic separation · CPC title

• B03C1/01

  by addition of magnetic adjuvants · CPC title