Biosensor utilizing a resonator having a functionalized surface

• US 7,871,569 B2
• Filed: 12/22/2005
• Issued: 01/18/2011
• Est. Priority Date: 12/30/2003
• Status: Expired due to Fees

• Current Assignee: Intel Corporation
• Original Assignee: Intel Corporation
• Inventors: Yamakawa, Mineo, Zhang, Yuegang, Wang, Li-Peng, Ma, Qing, Rao, Valluri, Berlin, Andrew A.
• Primary Examiner(s): Soderquist; Arlen
• Application Number:
  US11/317,518
• Publication Number:
  US 20060133953A1
• Time in Patent Office: 1,853 Days
• Field of Search: 422/50, 422/68.1, 422 8201- 8203, 422/61, 422/98, 436/501, 436/43, 436/63, 436 86- 87, 436 94- 95
• US Class Current: 422/68.1
• 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
• 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 system comprising:

(a) a film bulk acoustic piezoelectric resonator (FBAR) comprising a layer of piezoelectric material and a pair of electrodes coupled to the layer of piezoelectric material,

said FBAR being mounted on an insulator comprising a semiconductive layer and first and second, spaced apart insulating layers, said FBAR having a first edge contacting said first insulating layer and a second edge contacting said second insulating layer, wherein said semiconductive layer, said spaced apart insulating layers, and said FBAR define a void region therebetween,

wherein at least one surface of one of the electrodes or of the piezoelectric material is functionalized to bind with target molecules in a liquid sample; and

(b) a control circuit comprising a signal generating circuit to apply an excitation signal that includes a plurality of frequencies to the pair of electrodes and a processing circuit to measure the impedance of the resonator FBAR to the frequencies of the excitation signal, whereby the presence of the binding of the target molecule can be detected by observing an alteration in the frequency response of the resonator FBAR;

(c) a memory coupled to the processing circuit, the memory having a baseline response stored therein,

wherein the system is configured to detect the target molecule comprising a biological molecule.

2. The system of claim 1, wherein the excitation signal comprises a time variant, single frequency signal, whereby the plurality of frequencies is applied sequentially.

3. The system of claim 1, wherein the excitation signal comprises a mixed frequency signal, whereby the plurality of frequencies is applied simultaneously.

4. The system of claim 1, wherein the functionalized surface is a surface of the piezoelectric material.

5. The system of claim 1, wherein the functionalized surface is a surface of an electrode.

6. The system of claim 1, wherein the substrate comprises a silicon-containing substrate.

7. The system of claim 1, wherein the functionalized surface is functionalized with biologically active or derivatized material.

8. The system of claim 1, wherein the FBAR is coupled to the control circuit by the pair of electrodes.

9. The system of claim 1, wherein the FBAR has a fundamental resonance at a frequency at which a corresponding wavelength is twice the thickness of the piezoelectric layer.

10. The system of claim 1, wherein the FBAR has edges and further comprising a support structure wherein the FBAR is positioned with edges on the support structure.

11. The system of claim 10, further comprising a protective layer that covers the FBAR except the functionalized surface.

12. The system of claim 1, wherein the functionalized surface comprises molecules that bind with target molecules in a liquid sample.

13. The system of claim 1, wherein the exposed surface of the test FBAR electrode is functionalized with an ion selective membrane.

14. The system of claim 13, wherein the ion-selective membrane provides a transport mechanism.

15. The system of claim 1, wherein the electrodes comprise Al, Au, W, Pt or Mo.

16. The system of claim 1, wherein the piezoelectric material comprises AlN or ZnO.