Computer program and database structure for detecting molecular binding events

• US 6,395,480 B1
• Filed: 02/01/1999
• Issued: 05/28/2002
• Est. Priority Date: 02/01/1999
• Status: Expired due to Fees

• Current Assignee: Mds Sciex
• Original Assignee: Signature BioScience, Inc.
• Inventors: Hefti, John
• Primary Examiner(s): Brusca, John S.
• Assistant Examiner(s): KIM, YOUNG J
• Application Number:
  US09/243,196
• Publication Number:
  US 20020072857A1
• Time in Patent Office: 1,212 Days
• Field of Search: 435/6,7.1,7.2 204/403
• US Class Current: 435/6.11
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings

Abstract

Systems and methods for detecting molecular binding events and other environmental effects using the unique dielectric properties of the bound molecular structure or structures are presented. A molecular binding layer is coupled along the surface of a signal path. A test signal is propagated along the signal path, whereby the test signal couples to the molecular binding layer, and in response, exhibits a signal response.

Claims

1. A computer program product, on a computer readable storage medium, for controlling a molecular binding event detection system to detect one or more molecular binding events between a ligand and an antiligand, the molecular binding event detection system including a molecular binding layer coupled to a signal path, the computer program product comprising:

code that controls said molecular binding detection system to propagate a first test signal along said signal path, said signal path operable to support the propagation of electromagnetic signals at or above 10 MHz and comprising a transmission line, a ground element, and a dielectric layer interposed between said transmission line and said ground element, wherein said molecular binding layer is formed between at least a portion of said transmission line and at least a portion of said ground element and wherein said first test signal operates at one or more frequencies between 10 MHz and 1000 GHz, said first test signal electromagnetically couples to said molecular binding layer and exhibits a first signal response indicating detection of said binding event between said ligand and said antiligand.

2. The computer program product of claim 1, further comprising code that controls said molecular binding detection system to propagate a second test signal along said signal path, wherein said second test signal operates at one or more frequencies between 10 MHz and 1000 GHz, said second test signal electromagnetically couples to said molecular binding layer comprising said second antiligand, wherein said second test signal exhibits a second signal response indicating detection of said binding event between said second antiligand and said ligand.

6. The computer program product of claim 1, further comprising code that controls said molecular binding detection system to apply a first solution comprising said ligand to said molecular binding layer, said molecular binding layer comprising said antiligand.

7. The computer program product of claim 2, further comprising code that controls said molecular binding detection system to apply a second solution containing a second antiligand to said molecular binding layer, wherein said second antiligand binds to said ligand.

8. The computer program product of claim 1, wherein code that controls said molecular binding detection system to propagate a first test signal along said signal path comprises code that controls said molecular binding event detection system to transmit a signal at one or more frequencies from 10 MHz to 100 MHz.

9. The computer program product of claim 1, wherein code that controls said molecular binding detection system to propagate a first test signal along said signal path comprises code that controls said molecular binding event detection system to transmit a signal at one or more frequencies from 100 MHz to 1 GHz.

10. The computer program product of claim 1, wherein code that controls said molecular binding detection system to propagate a first test signal along said signal path comprises code that controls said molecular binding event detection system to transmit a signal at one or more frequencies from 1 GHz to 5 GHz.

11. The computer program product of claim 1, wherein code that controls said molecular binding detection system to propagate a first test signal along said signal path comprises code that controls said molecular binding event detection system to transmit a signal at one or more frequencies from 5 GHz to 10 GHz.

12. The computer program product of claim 1, wherein code that controls said molecular binding detection system to propagate a first test signal along said signal path comprises code that controls said molecular binding event detection system to transmit a signal at one or more frequencies from 10 GHz to 100 GHz.

13. The computer program product of claim 1, wherein said molecular binding region comprises a cell or a cell membrane.

14. The computer program product of claim 1, wherein said molecular binding region comprises an antibody.

3. A computer program product, on a computer readable storage medium, for controlling a molecular binding event detection system to quantify an unknown concentration of ligands in a solution, the molecular binding event detection system including a molecular binding layer coupled to a signal path, the computer program product comprising:

code that controls said molecular binding event detection system to propagate a first test signal along said signal path while said signal path is in contact with said solution, said signal path comprising a transmission line, a ground element and a dielectric layer interposed between the transmission line and the ground element, wherein said molecular binding layer is formed between at least a portion of said transmission line and at least a portion of said ground element, said first test signal operating at one or more frequencies between 10 MHz and 1000 GHz, said first test signal electromagnetically coupling to said molecular binding layer and providing a first signal response;

code that controls said molecular binding event detection system to correlate said first signal response to said first known concentration;

code that controls said molecular binding event detection system to propagate a second test signal along said signal path while said signal path is in contact with said solution, said second test signal operating at one or more frequencies between 10 MHz and 1000 GHz, said second test signal electromagnetically coupling to said molecular binding layer and providing a second signal response;

code that controls said molecular binding event detection system to generate an extrapolation algorithm of said solution based upon said first and second known concentrations and corresponding first and second signal responses;

code that controls said molecular binding event detection system to propagate a third test signal along said signal path while said signal path is in contact with said solution, said third test signal operating at one or more frequencies between 10 MHz and 1000 GHz, said third test signal electromagnetically coupling to said molecular binding layer and providing a third signal response; and

code that controls said molecular binding event detection system to apply said third signal response to said algorithm and to extrapolate said unknown concentration of said solution.

4. A computer program product, on a computer readable storage medium, for controlling a molecular binding event detection system to investigate binding of a ligand to an antiligand in a first aqueous solution containing or suspected of containing the ligand, the first aqueous solution optionally containing components other than said ligand, the computer program product comprising:

code that controls said molecular binding event detection system to transmit a first input signal along a signal path, said signal path comprising a transmission line, a ground element, and a dielectric layer interposed between the transmission line and a ground element, wherein said molecular binding layer is formed between at least a portion of said transmission line and at least a portion of said ground element and wherein said signal path is operable to support the propagation of electromagnetic signals at frequencies at or above 10 MHz, whereby said input signal operates at one or more frequencies between 10 MHz and 1000 GHz, said input signal electromagnetically coupled to said molecular binding layer while said first aqueous solution is in contact with said molecular binding layer;

code that controls said molecular binding event detection system to detect a first modulated signal after said first input signal has interacted with said molecular binding layer while in contact with said first aqueous solution;

code that controls said molecular binding event detection system to compare said first modulated signal to a baseline signal, said baseline signal operating at one or more frequencies between 10 MHz and 1000 GHz, said baseline signal having been obtained during interaction of an input signal with said molecular binding layer while in contact with a second aqueous solution, said second aqueous solution containing said optional components, if any, present in said first aqueous solution and further (a) containing said ligand, (b) containing a different ligand that binds to said antiligand, or (c) not containing any ligand that binds to said antiligand; and

code that controls said molecular binding event detection system to interpret similarity or difference of said first modulated signal to said baseline signal as an indication of degree or type of binding of said ligand to said antiligand.

15. The computer program product of claim 4, wherein code that controls said molecular binding detection system to propagate a first test signal along said signal path comprises code that controls said molecular binding event detection system to transmit a signal at one or more frequencies from 10 MHz to 100 MHz.

16. The computer program product of claim 4, wherein code that controls said molecular binding detection system to propagate a first test signal along said signal path comprises code that controls said molecular binding event detection system to transmit a signal at one or more frequencies from 100 MHz to 1 GHz.

17. The computer program product of claim 4, wherein code that controls said molecular binding detection system to propagate a first test signal along said signal path comprises code that controls said molecular binding event detection system to transmit a signal at one or more frequencies from 1 GHz to 5 GHz.

18. The computer program product of claim 4, wherein code that controls said molecular binding detection system to propagate a first test signal along said signal path comprises code that controls said molecular binding event detection system to transmit a signal at one or more frequencies from 5 GHz to 10 GHz.

19. The computer program product of claim 4, wherein code that controls said molecular binding detection system to propagate a first test signal along said signal path comprises code that controls said molecular binding event detection system to transmit a signal at one or more frequencies from 10 GHz to 100 GHz.

20. The computer program product of claim 4, wherein said molecular binding region comprises cell or a cell membrane.

21. The computer program product of claim 4, wherein said molecular binding region comprises antibody.

5. A computer program product, on a computer readable storage medium, for controlling a molecular binding event detection system to determine the classification of an unknown ligand, the computer program product comprising:

code that controls said molecular binding detection system to apply a solution containing a plurality of unknown ligands over a molecular binding layer, said molecular binding layer comprising a plurality of antiligands for binding a respective plurality of ligand sub-structures and said molecular binding layer electromagnetically coupled to a signal path, said signal path comprising a transmission line, a ground element, and a dielectric layer interposed between said transmission line and said ground element, wherein said molecular binding layer is formed between at least a portion of said electrically conductive transmission line and at least a portion of said ground element;

code that controls said molecular binding detection system to form a second molecular binding layer in response to said application of said solution, said second molecular binding layer comprising said plurality of antiligands and any of said unknown ligands that have bound to said plurality of antiligands;

code that controls said molecular binding detection system to propagate a plurality of electromagnetic test signals along said signal path to said second molecular binding layer, each of said electromagnetic test signals operating at one or more frequencies between 10 MHz and 1000 GHz, wherein each of said test signals couples to at least one of said plurality of antiligands that binds to one of said ligand substructures and in response exhibits a measured response indicative of the presence of binding of said antiligand to said sub-structure; and

code that controls said molecular binding detection system to retrieve known signal responses for comparison to said measured response, said known responses defining a known classification of ligands, wherein if a predetermined number of said known signal responses correlates within a predefined range with said measured responses, said unknown ligand is classified within said known classification.