Methods and systems for evaluating the length of elongated elements

• US 20070099191A1
• Filed: 11/01/2005
• Published: 05/03/2007
• Est. Priority Date: 11/01/2005
• Status: Active Grant

• Current Assignee: Georgia Institute of Technology (University System of Georgia)
• Original Assignee: Georgia Institute of Technology (University System of Georgia)
• Inventors: Nair, Sankar, Chatterjee, Abhijit, Bhattacharya, Soumendu, Natarajan, Vishwanath
• Granted Patent: US 7,835,870 B2
• Time in Patent Office: Days
• US Class Current: 435/6.12
• CPC Class Codes: C12Q 1/68 involving nucleic acids
• CPC Class Codes: C12Q 2525/204 specific length of the oligonucleotides
• CPC Class Codes: C12Q 2565/125 Electrophoretic separation
• CPC Class Codes: C12Q 2565/631 being a biochannel or pore

Abstract

Systems and methods are disclosed for evaluating the length of elongated elements in a sample. The disclosed systems and methods may include using a direct current stimulus to determine a direct current base length region corresponding to at least a portion of the sample. Furthermore, the disclosed systems and methods may include using an alternating current stimulus to determine that the direct current base length region corresponds to a first set of elongated elements and a second set of elongated elements. The first set of elongated elements may have a first base length and the second set of elongated elements may have a second base length. The elongated elements may comprise, for example, chain molecules, deoxyribonucleic acid (DNA), ribonucleic acid (RNA), or proteins. Furthermore, the disclosed systems and methods may include measuring an ion current through a nanopore, the ion current produced by the alternating current stimulus.

Claims

1. A method for evaluating the length of elongated elements in a sample, the method comprising:

using a direct current stimulus to determine a direct current base length region corresponding to at least a portion of the sample; and

using an alternating current stimulus to determine that the direct current base length region corresponds to a first set of elongated elements and a second set of elongated elements, the first set of elongated elements having a first base length and the second set of elongated elements having a second base length.

2. The method of claim 1, wherein using the alternating current stimulus to determine that the direct current base length region corresponds to the first set of elongated elements and the second set of elongated elements further comprises at least one of the first set of elongated elements and the second set of elongated elements comprising at least one of the following:

chain molecules, deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and proteins.

3. The method of claim 1, wherein using the alternating current stimulus to determine that the direct current base length region corresponds to the first set of elongated elements and the second set of elongated elements comprises measuring an ion current through a nanopore, the ion current produced by the alternating current stimulus.

4. The method of claim 1, wherein using the alternating current stimulus to determine that the direct current base length region corresponds to the first set of elongated elements and the second set of elongated elements comprises adjusting the alternating current stimulus to increase a difference between a mean translocation time corresponding to the first set of elongated elements and a mean translocation time corresponding to the second set of elongated elements.

5. The method of claim 4, wherein adjusting the alternating current stimulus comprises adjusting at least one of the following:

a frequency associated with the alternating current stimulus, an amplitude associated with the alternating current stimulus, and a phase associated with the alternating current stimulus.

6. The method of claim 4, wherein adjusting the alternating current stimulus comprises using a gradient search to optimize a set of parameters to produce a predetermined sensitivity value, the set of parameters comprising a frequency associated with the alternating current stimulus, an amplitude associated with the alternating current stimulus, and a phase associated with the alternating current stimulus.

7. The method of claim 6, wherein using the gradient search to optimize the set of parameters to produce the predetermined sensitivity value comprises setting the predetermined sensitivity value relative to a sensitivity value obtained using the direct current stimulus.

8. A system for evaluating the length of elongated elements in a sample, the system comprising:

a memory storage for maintaining a database; and

a processing unit coupled to the memory storage, wherein the processing unit is operative to;

use a direct current stimulus to determine a direct current base length region corresponding to at least a portion of the sample; and

use an alternating current stimulus to determine that the direct current base length region corresponds to a first set of elongated elements and a second set of elongated elements, the first set of elongated elements having a first base length and the second set of elongated elements having a second base length.

9. The system of claim 8, wherein the processing unit operative to use the alternating current stimulus to determine that the direct current base length region corresponds to the first set of elongated elements and the second set of elongated elements further comprises at least one of the first set of elongated elements and the second set of elongated elements comprising at least one of the following:

chain molecules, deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and proteins.

10. The system of claim 8, wherein the processing unit operative to use the alternating current stimulus to determine that the direct current base length region corresponds to the first set of elongated elements and the second set of elongated elements comprises the processing unit operative to measure an ion current through a nanopore, the ion current produced by the alternating current stimulus.

11. The system of claim 8, wherein the processing unit operative to use the alternating current stimulus to determine that the direct current base length region corresponds to the first set of elongated elements and the second set of elongated elements comprises the processing unit operative to adjust the alternating current stimulus to increase a difference between a mean translocation time corresponding to the first set of elongated elements and a mean translocation time corresponding to the second set of elongated elements.

12. The system of claim 11, wherein the processing unit operative to adjust the alternating current stimulus comprises the processing unit operative to adjust at least one of the following:

a frequency associated with the alternating current stimulus, an amplitude associated with the alternating current stimulus, and a phase associated with the alternating current stimulus.

13. The system of claim 11, wherein the processing unit operative to adjust the alternating current stimulus comprises the processing unit operative to use a gradient search to optimize a set of parameters to produce a predetermined sensitivity value, the set of parameters comprising a frequency associated with the alternating current stimulus, an amplitude associated with the alternating current stimulus, and a phase associated with the alternating current stimulus.

14. A computer-readable medium which stores a set of instructions which when executed performs a method for evaluating the length of elongated elements in a sample, the method executed by the set of instructions comprising:

using a direct current stimulus to determine a direct current base length region corresponding to at least a portion of the sample; and

using an alternating current stimulus to determine that the direct current base length region corresponds to a first set of elongated elements and a second set of elongated elements, the first set of elongated elements having a first base length and the second set of elongated elements having a second base length.

15. The computer-readable medium of claim 14, wherein using the alternating current stimulus to determine that the direct current base length region corresponds to the first set of elongated elements and the second set of elongated elements further comprises at least one of the first set of elongated elements and the second set of elongated elements comprising at least one of the following:

chain molecules, deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and proteins.

16. The computer-readable medium of claim 14, wherein using the alternating current stimulus to determine that the direct current base length region corresponds to the first set of elongated elements and the second set of elongated elements comprises measuring an ion current through a nanopore, the ion current produced by the alternating current stimulus.

17. The computer-readable medium of claim 14, wherein using the alternating current stimulus to determine that the direct current base length region corresponds to the first set of elongated elements and the second set of elongated elements comprises adjusting the alternating current stimulus to increase a difference between a mean translocation time corresponding to the first set of elongated elements and a mean translocation time corresponding to the second set of elongated elements.

18. The computer-readable medium of claim 17, wherein adjusting the alternating current stimulus comprises adjusting at least one of the following:

a frequency associated with the alternating current stimulus, an amplitude associated with the alternating current stimulus, and a phase associated with the alternating current stimulus.

19. The computer-readable medium of claim 17, wherein adjusting the alternating current stimulus comprises using a gradient search to optimize a set of parameters to produce a predetermined sensitivity value, the set of parameters comprising a frequency associated with the alternating current stimulus, an amplitude associated with the alternating current stimulus, and a phase associated with the alternating current stimulus.

20. The computer-readable medium of claim 19, wherein using the gradient search to optimize the set of parameters to produce the predetermined sensitivity value comprises setting the predetermined sensitivity value relative to a sensitivity value obtained using the direct current stimulus.