IP Library › Granted Patent US 12,287,350
Granted Patent B2
US 12,287,350 · App. 17/056,142 · Granted Apr 29, 2025

Sample analysis with mirrors

Inventors: Shencheng Ge (Boston, MA); Yunzhe Wang (Baltimore, MD); Nicolas J. Deshler (Berkeley, CA); Daniel J. Preston (Houston, TX); George M. Whitesides (Newton, MA)
Assignee: President and Fellows of Harvard College
G01N9/18
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Quick Facts
Patent No.
US 12,287,350
App. No.
17/056,142
Granted
Apr 29, 2025
Kind
B2
Abstract

A device is disclosed, including: a plate including a sample deposition tube adapted to receive a sample comprising one or more analytes, the sample deposition tube defining a vertical axis substantially perpendicular to a main surface of the plate; and a mirror positioned to project, substantially parallel to the main surface of the plate, an image of the sample deposition tube along its vertical axis, so as to allow determination of the vertical location of the one or more analytes inside the sample deposition tube. Methods for determining the density of one or more analytes using various embodiments of the device are also described.

Claims (30)

1. A device, comprising:

a plate comprising a sample deposition tube adapted to receive a sample comprising one or more analytes, the sample deposition tube defining a vertical axis substantially perpendicular to a main surface of the plate; and

a mirror positioned to project, substantially parallel to the main surface of the plate, an image of the sample deposition tube along its vertical axis, so as to allow determination of the vertical location of the one or more analytes inside the sample deposition tube.

2. The device of claim 1 , wherein the mirror is positioned at about 40° to about 50° with respect to the vertical axis substantially perpendicular to the main surface of the plate.

3. The device of claim 2 , wherein the mirror is positioned at about 45° with respect to the vertical axis substantially perpendicular to the main surface of the plate.

4. The device of claim 1 , further comprising a plurality of said sample deposition tubes and one or more said mirrors, wherein each one of the plurality of mirrors is positioned to project, substantially parallel to the main surface of the plate, an image of one or more of the plurality of the sample deposition tubes along the vertical axis substantially perpendicular to the main surface of the plate.

5. The device of claim 1 , further comprising an image-capturing device.

6. The device of claim 5 , wherein the image-capturing device comprises a flatbed scanner, a camera, or a combination thereof.

7. The device of claim 1 , further comprising one or more relay lenses configured to focus the projected image.

8. The device of claim 1 , wherein the main surface of the plate is defined by an x-axis and a y-axis, and wherein the plate comprises m sample deposition tubes arranged in a row along the x-axis, n sample deposition tubes arranged in a row along the y-axis, and a plurality of said mirrors each positioned to project, substantially parallel to the main surface of the plate, an image of one of the sample deposition tubes along its vertical axis.

9. The device of claim 8 , wherein m and n are 2 and 3, 3 and 4, 4 and 6, 6 and 8, 8 and 12, 16 and 24, or 32 and 48, respectively.

10. The device of claim 1 , wherein the plate comprises 6, 12, 24, 48, 96, 384, or 1536 said sample deposition tubes.

11. The device of claim 10 , wherein the plate comprises 96 said sample deposition tubes.

12. The device of claim 1 , further comprising a first magnet and a second magnet disposed adjacent to the sample deposition tube to impart a magnetic field that is inside the sample deposition tube; wherein each magnet comprises a first pole and a second pole, and the first pole of the first magnet faces the first pole of the second magnet.

13. The device of claim 12 , further comprising a third magnet disposed underneath the first magnet and a fourth magnet disposed underneath the second magnet; wherein each of the third and fourth magnets comprises a first pole and a second pole, and the second pole of the third magnet faces the second pole of the second magnet.

14. The device of claim 12 , further comprising a plurality of said sample deposition tubes and a plurality of said first and second magnets.

15. The device of claim 1 , wherein the sample comprises a paramagnetic medium.

16. The device of claim 15 , wherein the paramagnetic medium comprises a paramagnetic salt, a paramagnetic hydrophobic metal chelate, or a paramagnetic ionic liquid.

17. The device of claim 16 , wherein the paramagnetic salt comprises MnCl 2 , GdCl 3 , DyCl 3 , MnBr 2 , CuSO 4 , FeCl 2 , or HoCl 3 .

18. The device of claim 16 , wherein the metal chelate comprises gadopentetate dimeglumine (Gd⋅DTPA), gadodiamide, gadoversetamide, gadobenate dimeglumine, gadoxetate disodium, gadofosveset trisodium, gadoteridol, gadobutrol, or gadoterate meglumine.

19. The device of claim 16 , wherein the paramagnetic ionic liquid comprises [methyltrioctylammonium] 2 [MnCl 4 ], [methyltrioctylammonium] 3 [GdCl 6 ], [methyltrioctylammonium] 3 [HoCl 6 ], [methyltrioctylammonium] 3 [HoBr 6 ], [1-butyl-3-methyl imidazolium]3 [HoCl 6 ], [1-butyl-3-methyl imidazolium][FeCl 4 ], [1-butyl-2,3-dimethyl imidazolium]2 [MnCl 4 ], [1-butyl-2,3-dimethyl imidazolium] 3 [DyCl 6 ], [1-butyl-3-methyl imidazolium]3 [DyCl 6 ], [alanine methylester][FeCl 4 ], [alanine methylester] 2 [MnCl 4 ], [alanine methylester]3 [GdCl 6 ], [alanine methylester] 3 [HoCl 6 ], or [alanine methylester] 3 [DyCl 6 ].

20. The device of claim 1 , wherein the one or more analytes comprise a diamagnetic material.

21. The device of claim 1 , wherein the one or more analytes comprise molecules, particles, powders, emulsions, biological samples, or biological cells.

22. A method comprising:

providing a device comprising:

a plate comprising one or more sample deposition tubes adapted to receive one or more samples comprising one or more analytes, each of the one or more sample deposition tubes defining a vertical axis substantially perpendicular to a main surface of the plate; and

one or more mirrors positioned to project, substantially parallel to the main surface of the plate, an image of each of the one or more sample deposition tubes along its vertical axis, so as to allow determination of the vertical location of the one or more analytes inside each of the one or more sample deposition tubes;

depositing a sample comprising one or more analytes into one or more of the sample deposition tubes;

allowing the one or more analytes to migrate to a position at least partially determined by its density; and

projecting, substantially parallel to the main surface of the plate, an image of each of the one or more sample deposition tubes along its vertical axis to determine the vertical location of the one or more analytes inside each of the one or more sample deposition tubes.

Assignments (2)
CONFIRMATORY LICENSE Recorded May 27, 2022
From: HARVARD UNIVERSITY
To: UNITED STATES DEPARTMENT OF ENERGY
Reel/Frame 060205/0646 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 30, 2021
From: DESHLER, NICOLAS; GE, SHENCHENG; PRESTON, DANIEL JOHN; WANG, YUNZHE; WHITESIDES, GEORGE M.
To: PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Reel/Frame 055770/0974 →
Continuity (3)
Provisional Application 62681756 · Jun 7, 2018
Provisional Application 62673405 · May 18, 2018
Related Publication 20210341369A1 · Nov 4, 2021
References Cited (35)
US 3579306A · Crane · 1971 [cited by examiner]
US 6586193B2 · Yguerabide et al. · 2003 [cited by applicant]
US 7491366B2 · Tokhtuev · 2009 [cited by examiner]
US 7815858B2 · Sevigny et al. · 2010 [cited by applicant]
Larson et al. (Nature Protocols, 2014, 9(10):2317-2328) (Year: 2014). [cited by examiner]
Le et al. (Lab Chip, 2009, 9:244-250) (Year: 2009). [cited by examiner]
Andersen et al., “Detection of membrane-bound and soluble antigens by magnetic levitation,” Lab on a Chip, Sep. 5, 2017, vol. 17, pp. 3462-3473. [cited by applicant]
Benz et al., “Employing Magnetic Levitation to Monitor Reaction Kinetics and Measure Activation Energy,” Journal of Chemical Education, Apr. 6, 2012, vol. 89, pp. 776-779. [cited by applicant]
Bloxham et al., “Fractionating Polymer Microspheres as Highly Accurate Density Standards,” Analytical Chemistry, Jun. 19, 2015, vol. 87, pp. 7485-7491. [cited by applicant]
Bwambok et al., “Paramagnetic Ionic Liquids for Measurements of Density Using Magnetic Levitation,” Analytical Chemistry, Aug. 23, 2013, vol. 85, pp. 8442-8447. [cited by applicant]
Calleja, F. J. B., “Magnetic Susceptibility as an Application to the Study of Order-Disorder Phenomena in Polymers,” Journal of Polymer Science: Part C (1969), No. 16, pp. 4311-4321. [cited by applicant]
Cugat et al., “Magnetic Micro-Actuators and Systems (MAGMAS),” IEEE Transactions on Magnetics, Nov. 2003, vol. 39, pp. 3607-3612. [cited by applicant]
Durmus et al., “Magnetic levitation of single cells,” Proc. Natl. Acad. Sci., published online Jun. 29, 2015, vol. 112, E3661-E3668. [cited by applicant]
Fabry et al., “Dense Cells in Sickle Cell Anemia: The Effects of Gene Interaction,” Blood, Nov. 1984, vol. 64(5), pp. 1042-1046. [cited by applicant]
Ge et al., “Magnetic Levitation to Characterize the Kinetics of Free-Radical Polymerization,” J. Am. Chem. Soc., Dec. 6, 2017, vol. 139, pp. 18688-18697. [cited by applicant]
Grover et al., “Measuring single-cell density,” PNAS, Jul. 5, 2011, vol. 108(27), pp. 10992-10996. [cited by applicant]
International Search Report and Written Opinion mailed Sep. 18, 2019, in the International Application No. PCT/US19/32797. 15 pages. [cited by applicant]
Knowlton et al., “Sickle cell detection using a smartphone,” Scientific Reports, Oct. 22, 2015, vol. 5:15022, 11 pages. [cited by applicant]
Kumar et al., “Density-based separation in multiphase systems provides a simple method to identify sickle cell disease,” Proc. Natl. Acad. Sci., Oct. 14, 2014, vol. 111, pp. 14864-14869. [cited by applicant]
Lara et al., “Enrichment of rare cancer cells through depletion of normal cells using density and flow-through, immunomagnetic cell separation,” Experimental Hematology, Oct. 2004, vol. 32, pp. 891-904. [cited by applicant]
Mace et al., “Aqueous Multiphase Systems of Polymers and Surfactants Provide Self-Assembling Step-Gradients in Density,” J. Am. Chem. Soc., May 17, 2012, vol. 134, pp. 9094-9097. [cited by applicant]
McCloskey et al., “Magnetic Cell Separation: Characterization of Magnetophoretic Mobility,” Anal. Chem., published online Nov. 15, 2003, vol. 75, pp. 6868-6874. [cited by applicant]
Mirica et al., “Magnetic Levitation in the Analysis of Foods and Water,” Journal of Agricultural and Food Chemistry, published online May 13, 2010, vol. 58, pp. 6565-6569. [cited by applicant]
Mirica et al., “Measuring Densities of Solids and Liquids Using Magnetic Levitation: Fundamentals,” J. Am. Chem. Soc., published online Jul. 2, 2009, vol. 131, pp. 10049-10058. [cited by applicant]
Mirica et al., “Using Magnetic Levitation to Distinguish Atomic-Level Differences in Chemical Composition of Polymers, and to Monitor Chemical Reactions on Solid Supports,” JACS, Dec. 8, 2008, vol. 130, pp. 17678-17680. [cited by applicant]
Nakamura et al., “Differences in Behavior among the Chlorides of Seven Rare Earth Elements Administered Intravenously to Rats,” Fundamental and Applied Toxicology, Jun. 1997, vol. 37, pp. 106-116. [cited by applicant]
Nemiroski et al., “High-Sensitivity Measurement of Density by Magnetic Levitation,” Analytical Chemistry, Jan. 27, 2016, vol. 88, pp. 2666-2674. [cited by applicant]
Nemiroski et al., “Tilted Magnetic Levitation Enables Measurement of the Complete Range of Densities of Materials with Low Magnetic Permeability,” J. Am. Chem. Soc., Jan. 2016, vol. 138, pp. 1252-1257. [cited by applicant]
Pulko et al., “Magnetic separation of Dy(III) ions from homogeneous aqueous solutions,” Applied Physics Letters, published online Dec. 11, 2014, vol. 105:232407, 4 pages. [cited by applicant]
Shapiro et al., “Measuring Binding of Protein to Gel-Bound Ligands Using Magnetic Levitation,” J. Am. Chem. Soc., Feb. 24, 2012, vol. 134, pp. 5637-5646. [cited by applicant]
Sun et al., “Continuous, Flow-Through Immunomagnetic Cell Sorting in a Quadrupole Field,” Cytometry, Dec. 1998, vol. 33, pp. 469-475. [cited by applicant]
Tasoglu et al., “Magnetic Levitational Assembly for Living Material Fabrication,” Advanced Healthcare Materials, published online Apr. 14, 2015, vol. 4, pp. 1469-1476. [cited by applicant]
Thanki et al., “Photo-irradiation induced morphological changes in nylon 66,” Polymer, Jan. 2001, vol. 42, pp. 535-538. [cited by applicant]
Winkleman et al., “A magnetic trap for living cells suspended in a paramagnetic buffer,”. Applied Physics Letters, Sep. 20, 2004, vol. 85, pp. 2411-2413. [cited by applicant]
Xia et al., “Density measurement for polymers by magneto-Archimedes levitation: Simulation and experiments,” Polymer Testing, available online Sep. 11, 2017, vol. 63, pp. 455-461. [cited by applicant]