Thin film bulk acoustic resonator with signal enhancement
Sensitivity of thin film bulk acoustic resonance (TFBAR) sensors is enhanced by mass amplification and operating a high frequency.
1. A method for detecting an analyte in a sample, comprising:
contacting an analyte or an analyte and a tag-linked analyte molecule, a first recognition component, and an amplification element-linked second recognition component to generate a complex comprising the first recognition component, the analyte or tag-linked analyte molecule, and the amplification element-linked second recognition component,
wherein the first recognition component is immobilized relative to a surface of a Thin Film Bulk Acoustic Resonator (“TFBAR”) and is configured to selectively bind one or more of the analyte, the analyte molecule to which the tag is linked or the tag, or any one or more of these molecules bound to the second recognition component, wherein the TFBAR has a resonance band of about 2 GHz to about 10 GHz, and
wherein the amplification element-linked second recognition component is configured to selectively bind the analyte, the analyte molecule to which the tag is linked or the tag, or any one or more of these molecules bound to the first recognition component;
contacting the linked amplification element with an amplification precursor under conditions to convert the amplification precursor into a molecule that adds mass at a surface of the TFBAR; and
determining the mass added at the surface of the TFBAR.
2. The method of claim 1 , wherein the analyte or the analyte and the tag-linked analyte are contacted with the amplification element-linked second recognition component prior to contact with the first recognition component immobilized relative to the surface of the TFBAR.
3. The method of claim 1 , wherein the analyte or the analyte and the tag-linked analyte are contacted with the first recognition component prior to contact with the amplification element-linked second recognition component.
4. The method of claim 1 , wherein the analyte or the tag-linked analyte, the first recognition component and the amplification element-linked second recognition component are contacted simultaneously.
5. The method of claim 1 , wherein determining the mass added to or bound to the surface of the TFBAR comprises:
coupling an input electrical signal to the TFBAR, the input electric signal having an input frequency within the resonance band of the TFBAR;
transmitting the input electrical signal through or across the TFBAR to generate an output electrical signal;
receiving the output electrical signal from the TFBAR; and
determining a change in phase shift of the output electrical signal caused by deposition of the precipitate on the surface of the TFBAR.
6. The method of claim 5 , wherein the change in phase shift is a change in insertion or reflection coefficient phase shift.
7. The method of claim 1 , wherein measuring the mass added to or bound to the surface of the TFBAR comprises:
actuating the TFBAR into an oscillating motion at an actuation frequency of between 2 GHz to 10 GHz;
measuring one or more resonator output signals representing resonance characteristics of the oscillating motion of the TFBAR; and
adjusting the actuation frequency of the TFBAR to maintain a resonance point of the TFBAR.
8. The method of claim 7 , wherein the resonance point of the TFBAR is a point of maximum group delay.
9. The method of claim 5 , wherein the frequency is from about 2 GHz to about 2.5 GHz.
10. The method of claim 1 , wherein the amplification element is an enzyme and the amplification precursor is a substrate, and wherein the enzyme is configured to convert the substrate to a precipitate.
11. The method of claim 1 , wherein the TFBAR has a resonance band of about 2 GHz to about 4 GHz.
12. The method of claim 1 , wherein the TFBAR has a resonance band of about 2 GHz to about 3 GHz.
13. The method of claim 1 , wherein the TFBAR has a resonance band of about 2 GHz to about 2.5 GHz.
14. The method of claim 1 , wherein the TFBAR has a resonance band of about 2 GHz to about 2.4 GHz.
15. The method of claim 5 , wherein the input frequency is from about 2 GHz to about 4 GHz.