IP Library Granted Patent US 9,868,991
Granted Patent B2
US 9,868,991 · App. 13/637,645 · Granted Jan 16, 2018

Nanomotors and motion-based detection of biomolecular interactions

Inventors: Joseph Wang (San Diego, CA); Jie Wu (Nanjing, CN); Shankar Balasubramanian (Acton, MA); Daniel Kagan (Westfield, NJ); Kalayil Manian Manesh (San Diego, CA)
Assignee: The Regents of the University of California
C12Q1/6886C07K17/14C12N15/115C12Q1/6816G01N33/557G01N33/558G01N33/587B82Y15/00Y10S977/726Y10S977/773Y10S977/92
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Quick Facts
Patent No.
US 9,868,991
App. No.
13/637,645
Granted
Jan 16, 2018
Kind
B2
Abstract

Techniques and systems are disclosed for detecting biomolecular interactions based on the motion of nanomotors. In one aspect, a method of detecting biomolecular interactions based on a motion of a nanomachine includes functionalizing a nanomachine with a capture probe adapted to interact with biological targets; and detecting a presence of the biological targets in an environment based on a motion of the nanomachine.

Claims (42)

1. A system for detecting biomolecular interactions, comprising:

a plurality of nanomachines, wherein each nanomachine of the plurality of nanomachines is to include two or more segments including a cathode segment and an anode segment, wherein at least one segment includes a functionalized surface, the nanomachine including a capture probe attached to the functionalized surface of the nanomachine, wherein the capture probe includes a region to molecularly bind to a target biological molecule;

a fluid comprising a fuel substance and biomolecules including the target biological molecule, wherein the target biological molecule includes a complimentary region able to couple to the capture probe at the region of the capture probe;

a nanoparticle assembly including a silver nanoparticle coupled to a molecular binding agent,

wherein, when the nanomachines are present in the fluid, the capture probe is operable to form a complex with the nanoparticle assembly via the target biological molecule in the fluid on the nanomachine, and wherein the silver nanoparticle of the nanoparticle assembly catalyzes a reaction with the fuel substance to cause the nanomachine to autonomously move in the fluid; and

an optical microscope to measure the motion of the nanomachine, wherein the complex formation of the capture probe with the nanoparticle assembly and the target biological molecule is indicated by the motion of the nanomachine,

wherein the system is operable to detect binding of the target biological molecule to the capture probe and the nanoparticle assembly based on the motion of the nanomachine.

2. The system of claim 1 , wherein the system is configured to detect a concentration of a plurality of target biological molecules based on a distance traveled by the nanomachine.

3. The system of claim 1 , wherein the nanomachine is operable to move in the fluid based on the release of silver ions from the silver nanoparticle.

4. The system of claim 1 , wherein the anode segment comprises platinum, and the cathode segment comprises gold.

5. The system of claim 1 , wherein the target biological molecule comprises a nucleic acid.

6. The system of claim 1 , wherein the target biological molecule comprises a cancer biomarker.

7. The system of claim 1 , wherein the fuel substance includes hydrogen peroxide.

8. The system of claim 1 , wherein the capture probe includes a single-stranded oligonucleotide, an aptamer, or an antibody.

9. The system of claim 1 , wherein the surface of the at least one segment includes gold.

10. The system of claim 9 , wherein the capture probe includes a thiol region attachable to the gold surface of the nanomachine.

11. The system of claim 9 , wherein the functionalized surface includes mixed alkanethiol monolayers attached to the gold surface of the nanomachine.

12. The system of claim 9 , wherein the functionalized surface includes a molecular monolayers complex, comprising: a dithiothreitol (DTT), and a 6-mercapto-1-hexanol (MCH).

13. The system of claim 1 , wherein the nanomachine is operable to be steered by application of an external stimulus.

14. The system of claim 13 , wherein the nanomachine is operable to be steered by application of an electromagnetic energy pulse as the external stimulus.

15. The system of claim 13 , wherein the nanomachine is operable to be steered by application of a thermal energy pulse as the external stimulus.

16. The system of claim 13 , wherein the nanomachine is operable to be steered by application of an electrochemical reaction in the fluid as the external stimulus.

17. The system of claim 1 , wherein the motion of the nanomachine measured in the fluid corresponds to a concentration of the target biological molecule present in the fluid.

18. A system for detecting biomolecular interactions, comprising:

a fuel substance;

a nanomachine structured to include two or more segments including a cathode segment and an anode segment, wherein at least one segment includes a functionalized surface; and

a complex formed on the nanomachine operable to bind to a biological target and drive autonomous motion of the nanomachine in a fluid containing the fuel substance, the complex including:

a capture probe attached to the functionalized surface of the nanomachine, and

a nanoparticle assembly including a silver nanoparticle and a molecular binding agent, the nanoparticle assembly coupled to the capture probe by the biological target,

wherein the complex is structured to bind the biological target at a region of the capture probe having a molecular structure configured to molecularly couple to a complimentary molecular structure of the biological target, and

wherein the complex is structured to drive the nanomachine by a reaction of the fuel substance with the nanomachine based on catalysis of the silver nanoparticle,

wherein motion of the nanomachine measured in the fluid corresponds to a characteristic of the biological target present in the fluid.

19. A method for detecting biomolecular interactions based on nanomachine motility, the method comprising:

providing a fluid containing biomolecules including a biological target;

deploying, into the fluid:

a nanomachine structured to include two or more segments including a cathode segment and an anode segment, wherein at least one segment includes a functionalized surface,

a capture probe attached to the functionalized surface of the nanomachine, the capture probe including a region having a molecular structure configured to molecularly couple to a complimentary molecular structure of the biological target, and

a nanoparticle assembly including a silver nanoparticle and a molecular binding agent;

forming a complex on the nanomachine by coupling the nanoparticle assembly to the capture probe via the biological target;

adding a fuel substance to the fluid, wherein the complex on the nanomachine causes autonomous motion of the nanomachine based on a reaction of the fuel substance facilitated by catalysis of the silver nanoparticle in the fluid;

measuring, using an optical microscope, the motion of the nanomachine in the fluid; and

determining a characteristic of the biological target based on the measured motion of the nanomachine.

Assignments (2)
CONFIRMATORY LICENSE Recorded Jun 11, 2015
From: UNIVERSITY OF CALIFORNIA, SAN DIEGO
To: NATIONAL SCIENCE FOUNDATION
Reel/Frame 035822/0399 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 11, 2012
From: WANG, JOSEPH; WU, JIE; BALASUBRAMANIAN, SHANKAR; KAGAN, DANIEL; MANESH, KALAYIL MANIAN
To: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Reel/Frame 029449/0209 →
Continuity (2)
Provisional Application 61317963 · Mar 26, 2010
Related Publication 20130084569A1 · Apr 4, 2013