System and method for cell levitation and monitoring

Patent metadata

Field	Value
Publication number	US-12066445-B2
Application number	US-202117169765-A
Country	US
Kind code	B2
Filing date	Feb 8, 2021
Priority date	Feb 26, 2014
Publication date	Aug 20, 2024
Grant date	Aug 20, 2024

Abstract

Magnetic cell levitation and cell monitoring systems and methods are disclosed. A method for separating a heterogeneous population of cells is performed by placing a microcapillary channel containing the heterogeneous population of cells in a magnetically-responsive medium in the disclosed levitation system and separating the cells by balancing magnetic and corrected gravitational forces on the individual cells. A levitation system is also disclosed, having a microscope on which the microcapillary channel is placed and a set of two magnets between which the microcapillary channel is placed. Additionally, a method for monitoring cellular processes in real-time using the levitation system is disclosed.

First claim

What is claimed is:

1. A method for separating a heterogeneous population of cells, the method comprising the steps of:
placing a channel containing a sample of the heterogeneous population of cells in a magnetically-responsive medium into a levitation system, wherein the system comprises
a set of two magnets producing a magnetic field, wherein a space between the two magnets is sized to receive the channel; and
a microscopy device having a stage between the set of two magnets on which the channel is placed; and

levitating the heterogeneous population of cells in the magnetically-responsive medium by balancing a magnetic force applied to each of the cells by the magnetic field of the magnets with a corrected gravitational force of the cells in the magnetically-responsive medium, thereby separating the heterogeneous population of cells;
separating the individual cells to an equilibrium exhibiting a balance between only gravitational forces and magnetic forces on the individual cell; and
obtaining an image of the heterogeneous population of cells using the microscopy device and analyzing the image to characterize the heterogeneous population of cells.

2. The method of claim 1 , wherein the heterogeneous population of cells are differentiated from others in at least one of their magnetic susceptibility and cell density, and a cell variant creates this difference, wherein
the cell variant is selected from the group consisting of cell type, cell-cycle stage, malignancy, disease state, activation state, cellular age, infection state, cellular differentiation, apoptosis of the cell, and phagocytosis of the cell.

3. The method of claim 1 , wherein the heterogeneous population of cells is selected from a group consisting of red blood cells, leukocytes, lymphocytes, phagocytes, platelets, and cancer cells.

4. The method of claim 1 , wherein the levitation system comprises
a first mirror on a first open side of the channel and a second mirror on a second open side of the channel in which the mirrors are oriented at oblique angles relative to the path between the mirrors, and wherein
the method further comprises the step of reflecting light from a light source within the microscope with the first mirror through the sample of cells and towards the second mirror.

5. The method of claim 1 , wherein the microscopy device is an upright fluorescence microscope leveled horizontally on its side, a side-viewing microscope, a cell phone camera, a lensless charged-coupled device (CCD) or complementary metal-oxide semiconductor (CMOS) system, or an inverted microscope.

6. The method of claim 1 , wherein the magnetically-responsive medium is a paramagnetic medium and comprises gadolinium.

7. The method of claim 1 , wherein the method is performed at the point of care, and wherein the magnetic field does not interfere with mobile devices.

8. The method of claim 1 , wherein the magnetic field includes a magnetic field gradient created by electrical magnets using alternating currents.

9. The method of claim 1 , wherein the set of two magnets are permanent magnets in an anti-Helmholtz configuration.

10. The method of claim 1 , further comprising the step of observing the heterogeneous population of cells are in real time by the microscopy device, the microscopy device providing various images of the heterogeneous population of cells over a duration of time.

11. The method of claim 10 , further comprising the steps of altering a physical environment of the heterogeneous population of cells and of observing a response of the heterogeneous population of cells as a result of the physical environment.

12. The method of claim 10 , wherein individual cells in the heterogeneous population of cells are individually monitored and tracked during the step of observation.

13. The method of claim 10 , wherein the step of observation includes monitoring the heterogeneous population of cells during different phases of the cell life cycle.

14. The method of claim 10 , further comprising the steps of introducing a treatment agent into the heterogeneous population of cells and of observing a response of the heterogeneous population of cells as a result of the treatment agent.

15. The method of claim 14 , wherein observing a response of the heterogeneous population of cells as a result of the treatment agent includes monitoring a continued response of the heterogeneous population of cells to establish the emergence of resistance of the heterogeneous population of cells to the treatment agent.

16. The method of claim 1 , wherein the heterogeneous population of cells includes some cells that are infected with a virus.

17. The method of claim 1 , wherein the heterogeneous population of cells are levitated in a patient sample.

18. The method of claim 1 , wherein analyzing the image to characterize the heterogeneous population of cells involves evaluating morphological differences between the heterogeneous population of cells.

19. The method of claim 1 , wherein analyzing the image to characterize the heterogeneous population of cells involves producing a cell distribution profile over a range of levitational heights.

Assignees

• Brigham & Womens Hospital Inc
• Univ Leland Stanford Junior
• Beth Israel Deaconess Medical Ct Inc

Inventors

• Demirci Utkan
• Ghiran Ionita
• Tasoglu Savas
• Davis Ronald W
• Steinmetz Lars
• Durmus Naside Gozde
• Tekin Huseyin Cumhur

Classifications

• G01N33/575

  for cancer · CPC title

• G01N2800/7042

  Aging, e.g. cellular aging · CPC title

• G01N2800/52

  Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis · CPC title

• G01N2800/26

  Infectious diseases, e.g. generalised sepsis · CPC title

• G01N2800/042

  Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism · CPC title