Enzyme-encapsulated nanoparticle platform

Patent metadata

Field	Value
Publication number	US-10300152-B2
Application number	US-201415022551-A
Country	US
Kind code	B2
Filing date	Sep 17, 2014
Priority date	Sep 17, 2013
Publication date	May 28, 2019
Grant date	May 28, 2019

Abstract

Disclosed are methods, systems, and devices for implementing nanoparticles to encapsulate biomolecules such as enzymes. In one aspect, a nanoparticle device includes a shell structure including an internal layer structured to enclose a hollow interior region and include one or more holes penetrating through the internal layer, and an external layer formed of a porous material around the internal layer; and an enzyme contained within the interior region of the shell structure, the enzyme having entered the shell structure through the one or more holes and incapable of passing through the external layer, in which the pores are of a size that prevents the enzyme to pass through the pores while permitting substances smaller than the pore size to pass through the pores.

First claim

What is claimed is:

1. A nanoparticle sensor device for detecting an analyte, comprising:
enzyme-encapsulated nanoparticles capable of being injected into a living organism including a non-human animal or a human being, the enzyme-encapsulated nanoparticles structured to include:
a shell structure including an internal layer and an external layer, the internal layer enclosing a hollow interior region and structured to form one or more holes penetrating through the internal layer, and the external layer formed of a porous material arranged around the internal layer,
an enzyme contained within the interior region of the shell structure, wherein the internal layer is structured to form the one or more holes sized to allow the enzyme to pass through the internal layer, wherein the external layer is structured to prevent the enzyme from passing through the external layer but allow an analyte smaller than the enzyme to pass through the external layer, and wherein the enzyme is structured to catalyze the analyte that enters the interior region, and
a fluorophore attached to the shell structure and configured to emit an optical fluorescent signal based at least on the concentration of a chemical reactant or chemical product of a catalytic interaction of at least the enzyme and the analyte;

a light source to direct an excitation light through the skin of the living organism to cause emission of the optical fluorescent signal by the enzyme-encapsulated nanoparticles when located in a subcutaneous region of the living organism; and
an optical detector to detect the emitted optical fluorescent signal generated by the enzyme-encapsulated nanoparticle based on catalytic interaction between the enzyme and the analyte within the shell structure.

2. The device as in claim 1 , wherein the enzyme includes glucose oxidase (GLOX), the analyte includes glucose, and the fluorophore includes an oxygen-sensitive fluorophore including a ruthenium(II) or ruthenium(III) compound.

3. The device as in claim 2 , wherein the wavelength of the excitation light includes 450-550 nm.

4. The device as in claim 1 , further comprising:
a data processing unit in data communication with the optical detector to process the detected optical fluorescent signal as data and determine a concentration of the analyte in the living organism.

5. The device as in claim 4 , wherein the data processing unit is included in a mobile communication device including at least one of a smartphone, a tablet, or a wearable communication device.

6. The device as in claim 1 , wherein the enzyme-encapsulated nanoparticle includes a ligand molecule conjugated to the shell structure, the ligand molecule having an affinity to a receptor molecule of the living organism to attract the shell structure to the living organism.

7. The device as in claim 1 , wherein the enzyme-encapsulated nanoparticle is configured to a size capable of in vivo injection including in a range between 100 nm to 500 nm.

8. The device as in claim 1 , wherein the enzyme-encapsulated nanoparticle includes a paramagnetic material in the shell structure.

9. The device as in claim 1 , further comprising:
a patch or a band attachable to the living organism and including the optical detector to allow frequent measurement of the emitted optical fluorescent signal from the subcutaneous region through the skin of the living organism.

10. The device as in claim 9 , wherein the patch or band includes a flexible material including a fabric or polymer.

11. A nanoparticle sensor device for detecting an analyte, comprising:
enzyme-encapsulated nanoparticles capable of being injected into a biological system, the enzyme-encapsulated nanoparticles structured to include:
a shell structure including an internal layer and an external layer, the internal layer enclosing a hollow interior region and structured to form one or more holes penetrating through the internal layer, and the external layer formed of a porous material arranged around the internal layer,
glucose oxidase (GLOX) contained within the interior region of the shell structure, wherein the internal layer is structured to form the one or more holes sized to allow the GLOX to pass through the internal layer, wherein the external layer is structured to prevent the GLOX from passing through the external layer but allow glucose to pass through the external layer, and wherein the GLOX is structured to catalyze the glucose that enters the interior region, and
a fluorophore including a ruthenium(II) or ruthenium(III) compound attached to the shell structure and configured to emit an optical fluorescent signal based at least on the concentration of a chemical reactant or chemical product of a catalytic interaction of at least the GLOX and the glucose;

a light source to direct an excitation light to a region under an outer surface of the biological system to cause emission of the optical fluorescent signal by the enzyme-encapsulated nanoparticles when located in the region under the outer surface of the biological system, wherein the wavelength of the excitation light includes 450-550 nm; and
an optical detector to detect the emitted optical fluorescent signal generated by the enzyme-encapsulated nanoparticle based on catalytic interaction between the GLOX and the glucose within the shell structure.

12. The device as in claim 11 , further comprising:
a data processing unit in data communication with the optical detector to process the detected optical fluorescent signal as data and determine a concentration of the glucose in the biological system.

13. The device as in claim 12 , wherein the data processing unit is included in a mobile communication device including at least one of a smartphone, a tablet, or a wearable communication device.

14. The device as in claim 11 , wherein the enzyme-encapsulated nanoparticle includes a ligand molecule conjugated to the shell structure, the ligand molecule having an affinity to a receptor molecule of the biological system to attract the shell structure to the biological system.

15. The device as in claim 11 , wherein the enzyme-encapsulated nanoparticle is configured to a size capable of in vivo injection including in a range between 100 nm to 500 nm.

16. The device as in claim 11 , wherein the enzyme-encapsulated nanoparticle includes a paramagnetic material in the shell structure.

17. The device as in claim 11 , wherein the enzyme-encapsulated nanoparticles include a concentration of the GLOX in a range between 100 to 200 mg/mL.

18. The device as in claim 11 , further comprising:
a patch or a band attachable to the living organism and including the optical detector to allow frequent measurement of the emitted optical fluorescent signal through the skin of the living organism.

19. The device as in claim 18 , wherein the patch or band includes a flexible material including a fabric or polymer.

20. The device as in claim 11 , wherein the biological system includes a living organism including a non-human animal or a human being.

Assignees

• Univ California
• Devacell Inc

Inventors

• Ortac Inanc
• Esener Sadik C
• Yayla Ibrahim Gokce
• Messmer Bradley

Classifications

• A61K38/50

  acting on carbon-nitrogen bonds, other than peptide bonds (3.5), e.g. asparaginase · CPC title

• A61K49/0093 Primary

  Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle · CPC title

• A61B2503/40

  Animals · CPC title

• A61K9/5115

  Inorganic compounds · CPC title

• A61B5/14532

  for measuring glucose, e.g. by tissue impedance measurement · CPC title