Low cost, portable sensor for molecular assays

• US 9,599,591 B2
• Filed: 11/17/2011
• Issued: 03/21/2017
• Est. Priority Date: 03/06/2009
• Status: Active Grant

• Current Assignee: California Institute of Technology
• Original Assignee: California Institute of Technology
• Inventors: Pai, Alex H., Chapman, Stephen A., Hajimiri, Seyed Ali
• Primary Examiner(s): Crawford, Erik B
• Application Number:
  US13/299,087
• Publication Number:
  US 20120149129A1
• Time in Patent Office: 1,951 Days
• Field of Search: 737/79, 435/6.1, 435/6.11, 435/287.2, 436/526, 436/806, 299/779
• US Class Current: 1/1
• CPC Class Codes: C12Q 1/6825 Nucleic acid detection involving sensors
• CPC Class Codes: C12Q 1/6834 Enzymatic or biochemical coupling of nucleic acids to a solid phase
• CPC Class Codes: C12Q 2523/303 Applying a physical force on a nucleic acid
• CPC Class Codes: C12Q 2525/301 Hairpin oligonucleotides
• CPC Class Codes: C12Q 2563/143 Magnetism, e.g. magnetic label
• CPC Class Codes: G01N 27/3278 involving nanosized elements, e.g. nanogaps or nanoparticles nanopores G01N33/48721; magnetic beads G01N27/745
• CPC Class Codes: 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

Abstract

An integrated sensor that is capable of discriminating the distance of a label from the sensor without using an optical signal. The label is attached to a single probe molecule or a group of probe molecules that interacts with a single or group of target molecules. As a consequence of this interaction, the probe molecule and/or the target molecule undergo a conformal change. This conformal change leads to perturbations in the distance of the label from the sensor. Thus, measurements and properties such as the concentration and the identity of one or more target molecules can be discerned from signals generated by the sensor (or by a plurality of sensors in a sensor array) and subjected to analysis using general purpose programmable computers programmed with suitable software that controls the analytical process, and such measurements and properties can be provided as a result of the analysis.

Claims

1. A non-optical chemical sensor system, comprising:

a sensor structure having a surface, said sensor structure configured to measure a distance of a label from said sensor structure surface based on a change in frequency associated with the sensor structure;

a tether comprising a probe strand of a chemical substance having binding sites disposed along a length of said probe strand, said probe strand having a first end attached to said surface of said sensor structure and having a second end;

a control and analysis module connected to said sensor structure, said control and analysis module configured to control a non-optical measurement signal applied to said sensor structure and to analyze a measurement signal generated by said sensor structure; and

said label, wherein said tether is configured to tether said label to said sensor structure surface in the presence of a target chemical compound, and wherein said sensor structure is configured to non-optically sense said label;

wherein said control and analysis module is programmed to provide a measurement result indicative of the presence of said target chemical compound, said measurement result based on a first measurement of a distance of said label from said surface of said sensor in the absence of said target chemical compound and a second measurement of said distance of said label from said surface of said sensor in the presence of said target chemical compound.

2. The non-optical chemical sensor system of claim 1, wherein said label is connected to said second end of said tether.

3. The non-optical chemical sensor system of claim 1, wherein said non-optical measurement signal is an electrical signal.

4. The non-optical chemical sensor system of claim 1, wherein said label is configured to be subjected to a deliberately applied force.

5. The non-optical chemical sensor system of claim 1, wherein said probe strand comprises a ribonucleic acid.

6. The non-optical chemical sensor system of claim 1, wherein said probe strand comprises a polymer.

7. The non-optical chemical sensor system of claim 1, wherein said sensor structure comprises an LC oscillator, and wherein said frequency is a resonant frequency of said LC oscillator.

8. The non-optical chemical sensor system of claim 1, wherein said tether is configured such that said label is untethered from said sensor structure surface in the absence of said target chemical compound.

9. A non-optical method of performing a chemical assay, comprising:

providing the non-optical chemical sensor system of claim 1;

making said first measurement of said distance of said label from said surface of said sensor based on the change in frequency associated with the sensor structure in the absence of a specimen of interest;

applying a fluid comprising said target chemical compound to be identified to said non-optical chemical sensor system;

making said second measurement of said distance of said label from said surface of said sensor based on a said change in frequency associated with the sensor structure in the presence of said specimen of interest;

providing a measurement result indicative of the presence of said target chemical compound in said specimen of interest, said measurement result based on said first measurement and said second measurement; and

performing at least one of recording said result, transmitting said result to a data handling system, or displaying said result to a user.

10. The non-optical method of performing the chemical assay of claim 9, wherein said label is connected to said second end of said tether.

11. The non-optical method of performing the chemical assay of claim 9, wherein said non-optical measurement signal is a magnetic signal.

12. The non-optical method of performing the chemical assay of claim 9, wherein said non-optical measurement signal is an electrical signal.

13. The non-optical method of performing the chemical assay of claim 9, wherein the sensor structure comprises an LC oscillator.

14. The non-optical method of performing the chemical assay of claim 9, wherein said label is configured to be subjected to a deliberately applied force.

15. The non-optical method of performing the chemical assay of claim 9, wherein said probe strand comprises a ribonucleic acid.

16. The non-optical method of performing the chemical assay of claim 9, wherein said probe strand comprises a polymer.

17. The non-optical chemical sensor system of claim 1, wherein said sensor structure comprises an LC oscillator, and wherein said frequency is a resonant frequency of said LC oscillator.

18. A non-optical chemical sensor system, comprising:

a sensor structure having a surface, said sensor structure configured to measure a distance of a label from said sensor structure surface based on a change in frequency associated with the sensor structure;

a tether comprising a probe strand of a chemical substance having binding sites disposed along a length of said probe strand, said probe strand having a first end attached to said surface of said sensor structure and having a second end;

a control and analysis module connected to said sensor structure, said control and analysis module configured to control a non-optical measurement signal applied to said sensor structure and to analyze a measurement signal generated by said sensor structure; and

said label, wherein said tether is configured to tether said label to said sensor structure surface in the presence of a target chemical compound, wherein said tether is configured to tether said label to said sensor structure surface in the absence of said target chemical compound, and wherein said sensor structure is configured to non-optically sense said label,

wherein said control and analysis module is configured to provide a measurement result indicative of the presence of said target chemical compound, said measurement result based on a first measurement of a distance of said label from said surface of said sensor in the absence of said target chemical compound and a second measurement of said distance of said label from said surface of said sensor in the presence of said target chemical compound.

19. The non-optical chemical sensor system of claim 18, wherein said non-optical measurement signal is a magnetic signal.