IP Library Granted Patent US 11,262,355
Granted Patent B2
US 11,262,355 · App. 16/708,302 · Granted Mar 1, 2022

System and apparatus for porously-encapsulated magnetic-nanoparticle biosensors

Inventors: John B. Weaver (Hanover, NH); Barjor Gimi (Jamaica Plain, MA); Karl Griswold (Lyme, NH)
Assignee: THE TRUSTEES OF DARTMOUTH COLLEGE
G01N33/54366A61B5/055G01N27/745G01N33/54326G01R33/1269
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Quick Facts
Patent No.
US 11,262,355
App. No.
16/708,302
Granted
Mar 1, 2022
Kind
B2
Abstract

A system for measuring analyte concentrations has porous-walled nanocontainers containing multiple magnetic nanoparticles, the magnetic nanoparticles coated with a selective binder that is analyte-responsive and binds a the analyte, an indicator substance releasable from the selective binder by the analyte, or an indicator substance cleavable by the analyte, apparatus for exposing the nanocontainers to a fluid potentially containing the analyte, and magnetic spectroscopy of Brownian motion sensing apparatus for detecting agglutination of the nanoparticles or binding of analyte to the nanoparticles. The system is used in a method comprising coating magnetic nanoparticles with a selective binder, encapsulating the magnetic nanoparticles in porous nanocontainers, exposing the nanocontainers to a fluid potentially containing analyte, using magnetic spectroscopy of Brownian motion sensing apparatus to detect agglutination or binding of the nanoparticles, and translating Brownian motion spectra to analyte concentrations.

Claims (29)

1. A system for measuring an analyte concentration in a solution comprising:

a plurality of nanocontainers having porous walls, the nanocontainers containing a plurality of magnetic nanoparticles, the magnetic nanoparticles coated with a selective binder capable of selectively binding a substance selected from the group consisting of the analyte, an indicator substance releasable from the selective binder by the analyte, and an indicator substance cleavable by the analyte;

apparatus for exposing the nanocontainers to the solution; and

magnetic spectroscopy of Brownian motion (MSB) sensing apparatus for detecting agglutination or aggregation of the nanoparticles;

wherein the selective binder capable of selectively binding a substance is selected from the group consisting of a nucleic acid strand, a protein, and a combination of nucleic acid strands and protein;

wherein the nanocontainers are nanocontainers having average size less than 150 microns in largest dimension;

the MSB sensing apparatus comprising:

apparatus configured to drive a drive coil adapted to provide an alternating magnetic field at a drive frequency to the magnetic nanoparticles, a pickup coil and a reverse-wound balancing coil configured to sense a response induced in the magnetic field by the magnetic nanoparticles,

the pickup coil and balancing coil coupled through an amplifier to a processor, the processor configured to measure harmonics of the drive frequency.

2. The system of claim 1 wherein the drive frequency is swept across a plurality of measured frequencies in a range of frequencies while responses are measured at each measured frequency to obtain a spectrum of responses induced in the magnetic field by the magnetic nanoparticles.

3. The system of claim 2 , further comprising bias field magnets configured to apply a bias field to a living mammal, and wherein the bias field is swept to map both magnetic nanoparticle concentration and analyte concentration at multiple positions within the living mammal, where the apparatus for exposing the nanocontainers to the solution comprises apparatus for injecting the nanocontainers into the living mammal.

4. The system of claim 2 , where the apparatus for exposing the nanocontainers to the solution comprises a test plate to which nanocontainers are adhered.

5. The system of claim 4 where the selective binder capable of selectively binding a substance is a nucleic-acid chain.

6. The system of claim 4 , where the selective binder capable of selectively binding a substance is a protein.

7. The system of claim 6 where the selective binder capable of selectively binding a substance is an antibody.

8. The system of claim 3 where the selective binder capable of selectively binding a substance is a nucleic-acid chain.

9. The system of claim 7 , where the selective binder capable of selectively binding a substance is a protein.

10. The system of claim 6 where the selective binder capable of selectively binding a substance is an antibody.

11. The system of claim 2 , where the apparatus for exposing the nanocontainers to the solution comprises apparatus for injecting the nanocontainers into a living mammal.

12. The system of claim 1 , where the apparatus for exposing the nanocontainers to the solution comprises a test plate to which nanocontainers are adhered.

13. The system of claim 12 where the selective binder capable of selectively binding a substance is a nucleic-acid chain.

14. The system of claim 12 , where the selective binder capable of selectively binding a substance is a protein.

15. The system of claim 14 where the selective binder capable of selectively binding a substance is an antibody.

16. The system of claim 1 where the selective binder capable of selectively binding a substance is a nucleic-acid chain.

17. The system of claim 1 , where the selective binder capable of selectively binding a substance is a protein.

18. The system of claim 17 where the selective binder capable of selectively binding the analyte is an antibody.

19. The system of claim 1 wherein the nanocontainers are fabricated from photoresist.

20. The system of claim 19 wherein the photoresist comprises polymethyl methacrylate.

21. The system of claim 2 further comprising bias field magnets configured to apply a bias field to a living mammal, and wherein the bias field is swept to map both magnetic nanoparticle concentration and analyte concentration at multiple positions within the living mammal.

Continuity (3)
Continuation 14408041
Provisional Application 61659788 · Jun 14, 2012
Related Publication 20200110085A1 · Apr 9, 2020