# US 10,502,735 B2 · System and apparatus for porously-encapsulated magnetic-nanoparticle biosensors

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- Number: US 10,502,735 B2
- Document ID: US10502735B2
- Status: Granted
- Kind: B2
- Application number: 14/408,041
- Filed: 2013-06-14
- Published: 2015-05-28
- Granted: 2019-12-10
- Earliest claimed: 2012-06-14
- Assignees: Trustees of Dartmouth College
- Applicants: The Trustees of Dartmouth College
- Inventors: John B. Weaver; Barjor Gimi; Karl Griswold
- Web page: https://patentgrep.com/patent/US10502735B2

## CPC

- G01N 33/54366: {Apparatus specially adapted for solid-phase testing}
- A61B 5/055: involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
- G01N 27/745: {for detecting magnetic beads used in biochemical assays (concerning the assays G01N33/54326; sensors therefor G01R33/1269; automatic analysers therefor G01N35/0098)}
- G01N 33/54326: {Magnetic particles}
- G01R 33/1269: {of molecules labeled with magnetic beads (magnetic particles for bio assay G01N33/54326)}
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- G01R: MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES (indicating correct tuning of resonant circuits H03J3/12)

## 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

### Claim 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 sensing apparatus for detecting agglutination or aggregation of the nanoparticles;
wherein the selective binder capable of selectively binding the analyte 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; and
where the nanocontainers are formed of an alginate.

### Claim 2 (depends on 1)

The system of claim 1, where the apparatus for exposing the nanocontainers to the solution comprises apparatus for injecting the nanocontainers into a living mammal.

### Claim 3 (depends on 1)

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

### Claim 4 (depends on 1)

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

### Claim 5 (depends on 1)

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

### Claim 6 (depends on 1)

The system of claim 1 where the selective binder capable of selectively binding the analyte is an antibody.

### Claim 7

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 sensing apparatus for detecting agglutination or aggregation of the nanoparticles;
wherein the selective binder capable of selectively binding the analyte 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 are less than one millimeter in largest dimension; and
where the apparatus for exposing the nanoparticles to the solution comprises a well of a multiple-test plate within which the nanocontainers containing the nanoparticles are deposited.