Biosensor utilizing a resonator having a functionalized surface

• US 20050148065A1
• Filed: 12/30/2003
• Published: 07/07/2005
• Est. Priority Date: 12/30/2003
• Status: Abandoned Application

• Current Assignee: Intel Corporation
• Original Assignee: Intel Corporation
• Inventors: Yamakawa, Mineo, Zhang, Yuegang, Wang, Li-Peng, Ma, Qing, Rao, Valluri, Berlin, Andrew A.
• Application Number:
  US10/749,529
• Publication Number:
  US 20050148065A1
• Time in Patent Office: Days
• US Class Current: 435/287.200
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: G01N 2291/02466 Biological material, e.g. blood
• CPC Class Codes: G01N 2291/0255 (Bio)chemical reactions, e.g. on biosensors
• CPC Class Codes: G01N 2291/0256 Adsorption, desorption, surface mass change, e.g. on biosensors
• CPC Class Codes: G01N 2291/0426 Bulk waves, e.g. quartz crystal microbalance, torsional waves
• CPC Class Codes: G01N 27/126 comprising organic polymers
• CPC Class Codes: G01N 29/022 Fluid sensors based on microsensors, e.g. quartz crystal-microbalance [QCM], surface acoustic wave [SAW] devices, tuning forks, cantilevers, flexural plate wave [FPW] devices microdevices per se B81B
• CPC Class Codes: G01N 29/036 by measuring frequency or resonance of acoustic waves
• CPC Class Codes: G01N 29/2437 Piezoelectric probes
• CPC Class Codes: G01N 29/348 with frequency characteristics, e.g. single frequency signals, chirp signals measuring frequency of mechanical vibrations or acoustic waves in general G01H1/06, G01H3/04; measuring frequency or analysing frequency spectra G01R23/00
• CPC Class Codes: G01N 33/0031 comprising two or more sensors, e.g. a sensor array electrochemical electrode arrays G01N27/27
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: Y10T 436/11 Automated chemical analysis
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]
• CPC Class Codes: Y10T 436/144444 Glucose
• CPC Class Codes: Y10T 436/25375 Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]

Abstract

Systems and methods for detecting the presence of biomolecules in a sample using biosensors that incorporate resonators which have functionalized surfaces for reacting with target biomolecules. In one embodiment, a device includes a piezoelectric resonator having a functionalized surface configured to react with target molecules, thereby changing the mass and/or charge of the resonator which consequently changes the frequency response of the resonator. The resonator'"'"'s frequency response after exposure to a sample is compared to a reference, such as the frequency response before exposure to the sample, a stored baseline frequency response or a control resonator'"'"'s frequency response.

Claims

1. A device comprising:

a resonator;

wherein the resonator has at least one functionalized surface, wherein the functionalized surface is configured to react with target molecules.

2. The device of claim 1, wherein the resonator comprises a piezoelectric resonator, wherein the device further comprises a pair of electrodes coupled to the piezoelectric resonator and control circuitry configured to apply an excitation signal to the pair of electrodes and to determine a frequency response for the layer of piezoelectric material.

3. The device of claim 2, further comprising a second piezoelectric resonator having a non-functionalized surface and an additional pair of electrodes coupled to the second piezoelectric resonator, wherein the control circuitry is configured to apply the excitation signal to the additional pair of electrodes and to determine a frequency response for the second piezoelectric resonator.

4. The device of claim 3, wherein the piezoelectric resonators comprise film bulk acoustic resonators (FBARs).

5. The device of claim 2, wherein the excitation signal comprises an in-phase signal.

6. The device of claim 2, wherein the excitation signal comprises an out-of-phase signal.

7. The device of claim 2, wherein the excitation signal comprises a single frequency signal.

8. The device of claim 2, wherein the excitation signal comprises a mixed frequency signal.

9. The device of claim 2, wherein the excitation signal comprises a time-variant signal.

10. The device of claim 1, wherein the functionalized surface comprises one or more biomolecules configured to bind with the target molecules.

11. The device of claim 10, wherein the biomolecules comprise biologically active molecules.

12. The device of claim 10, wherein the biomolecules comprise biologically derivatized molecules.

13. The device of claim 1, wherein the functionalized surface is functionalized by immobilization of biomolecules on a self-assembly monolayer.

14. The device of claim 1, wherein the functionalized surface is functionalized by immobilization of biomolecules on an organic membrane.

15. The device of claim 14, wherein the organic membrane is pre-coated onto the functionalized surface.

16. The device of claim 14, wherein the organic membrane is chemically derivatized on the functionalized surface.

17. The device of claim 16, wherein the organic membrane is chemically derivatized on the functionalized surface by silylation.

18. The device of claim 16, wherein the organic membrane is chemically derivatized on the functionalized surface by acylation.

19. The device of claim 16, wherein the organic membrane is chemically derivatized on the functionalized surface by esterification.

20. The device of claim 16, wherein the organic membrane is chemically derivatized on the functionalized surface by alkylation.

21. The device of claim 1, wherein the functionalized surface is functionalized by direct immobilization of biomolecules on metal.

22. The device of claim 1, wherein the functionalized surface is functionalized by direct immobilization of biomolecules on a non-metallic inorganic film.

23. The device of claim 1, wherein the functionalized surface is functionalized by self-assembling biomolecular layers on the functionalized surface.

24. The device of claim 23, wherein the assembling biomolecular layers comprise amino acid derivatized fatty acids or lipids.

25. A. system comprising:

a layer of piezoelectric material, wherein the layer of piezoelectric material has at least one surface that is functionalized to bind with target molecules

a pair of electrodes coupled to the layer of piezoelectric material

control circuitry configured to apply an excitation signal to the pair of electrodes and to determine a frequency response for the layer of piezoelectric material

26. A system comprising:

a pair of film bulk acoustic resonators (FBARs), including a test FBAR and a reference FBAR, wherein each FBAR includes

a layer of piezoelectric material

a pair of electrodes coupled to opposite sides of the layer of piezoelectric material;

wherein an exposed surface of one of the electrodes of the test FBAR is functionalized with biomolecules;

further comprising control circuitry coupled to the pair of FBARs and configured to determine frequency responses for the test FBAR and reference FBAR.

27. A method for detecting target molecules comprising:

providing a first resonator, wherein the first resonator has a first surface functionalized with a first type of biomolecules, wherein the presence of target molecules causes the first type of biomolecules to change the frequency response of the first resonator;

exposing the first surface of the first resonator to a test fluid;

determining a frequency response of the first resonator after the first surface has been exposed to the test fluid; and

determining, based upon the frequency response of the first resonator, whether the test fluid contained target molecules.

28. The method of claim 27, further comprising:

providing a second resonator, wherein the second resonator has a second surface that is not functionalized with the first type of biomolecules;

exposing the second surface of the second resonator to the test fluid;

determining a frequency response of the second resonator after the second surface has been exposed to the test fluid; and

wherein determining, based upon the frequency response of the first resonator, whether the test fluid contained target molecules.

29. The method of claim 28, further comprising, after exposing the first surface of the first resonator and the second surface of the second resonator to the test fluid, removing at least a portion of the test fluid from the first surface of the first resonator and the second surface of the second resonator before determining the frequency responses of the first and second resonators.

30. The method of claim 28, further comprising, after exposing the first surface of the first resonator and the second surface of the second resonator to the test fluid, removing substantially all of the test fluid from the first surface of the first resonator and the second surface of the second resonator before determining the frequency responses of the first and second resonators.