Bulk acoustic wave resonator with increased dynamic range
Devices that include a low sensitivity bulk acoustic wave (BAW) resonator sensor including a surface to which a low recognition component is immobilized, the low recognition component being configured to selectively bind the analyte, an analyte molecule to which a tag is linked, or a tag, or any one of these molecules to which an amplification element-linked second recognition component is bound; a high sensitivity BAW resonator sensor including a surface to which a high recognition component is immobilized, the high recognition component being configured to selectively bind the analyte, an analyte molecule to which a tag is linked, or a tag, or any one of these molecules to which an amplification element-linked second recognition component is bound; one or more containers housing an amplification molecule, the amplification element-linked second recognition component, and optionally one or both of the tag and the analyte molecule.
1. A system for detecting an analyte in a sample, comprising:
a first bulk acoustic wave (BAW) resonator sensor comprising a surface to which a first recognition component is immobilized,
the first recognition component being configured to selectively bind: (a) the analyte, (b) an analyte molecule to which a tag is linked, (c) a tag, or (d) any combination thereof, to which an amplification element-linked recognition component is bound;
a second BAW resonator sensor comprising a surface to which a second recognition component is immobilized,
the second recognition component being configured to selectively bind: (a) the analyte, (b) an analyte molecule to which a tag is linked, (c) a tag, or (d) any combination thereof, to which an amplification element-linked recognition component is bound;
wherein the first recognition component has an affinity, capacity, or combination thereof for binding: (a) the analyte, (b) the analyte molecule to which the tag is linked, (c) the tag, or (d) any combination thereof, that is different from the affinity, capacity, or any combination thereof for binding: (a) the analyte, (b) the analyte molecule to which the tag is linked, (c) the tag, or (d) any combination thereof, of the second recognition component;
one or more containers housing an amplification element, a recognition component of the amplification element-linked recognition component, the tag, the analyte, or any combination thereof;
a fluid path from the one or more containers to the surface of both the first and second BAW resonator sensors to which the first and second recognition components are bound;
actuation circuitry configured to drive the first and second BAW resonator sensors in an oscillating motion;
measurement circuitry arranged to be coupled to both the first and second BAW resonator sensors and configured to measure one or more resonator output signals representing resonance characteristics of the oscillating motion of the low and high BAW resonator sensors; and
a controller operatively coupled with the actuation circuitry and the measurement circuitry.
2. The system of claim 1 , wherein the first and second recognition components are different.
3. The system of claim 2 , wherein the first recognition component has an affinity for binding: (a) the analyte, (b) the analyte molecule to which the tag is linked, (c) the tag, or (d) any combination thereof, that is lower than an affinity of the second recognition component for binding: (a) the analyte, (b) the analyte molecule to which the tag is linked, (c) the tag, or (d) any combination thereof.
4. The system of claim 1 , wherein the first and second recognition components are the same and wherein the first recognition component has a concentration on the surface of the first BAW resonator sensor to which it is immobilized that is different from a concentration of the second recognition component on the surface of the second BAW resonator sensor to which it is immobilized.
5. The system of claim 1 , wherein the controller utilizes the output signal from the first BAW resonator sensor, the second BAW resonator sensor, or both.
6. The system of claim 1 , wherein the controller utilizes the output signal from the first BAW resonator sensor, or the second BAW resonator sensor, but not both.
7. The system of claim 1 , wherein the controller utilizes both the output signal from the first BAW resonator sensor and the second BAW resonator sensor.
8. The system of claim 1 , wherein an amplification element of the amplification element-linked recognition component is configured to contact an amplification precursor and convert the amplification precursor into a molecule that adds mass at the surface of the first BAW resonator sensor, the second BAW resonator sensor, or both.
9. The system of claim 8 , wherein the amplification element comprises an enzyme and the amplification precursor comprises a substrate, and wherein the enzyme is configured to convert the substrate to a precipitate that adds mass at the surface of the first BAW resonator sensor, the second BAW resonator sensor, or both.
10. A kit for use with a device for detecting an analyte in a sample, comprising:
a system comprising:
a first bulk acoustic wave (BAW) resonator sensor comprising a surface to which a first recognition component is immobilized,
the first recognition component being configured to selectively bind: (a) the analyte, (b) an analyte molecule to which a tag is linked, (c) a tag, or (d) any combination thereof, to which an amplification element-linked recognition component is bound;
a second BAW resonator sensor comprising a surface to which a second recognition component is immobilized,
the second recognition component being configured to selectively bind: (a) the analyte, (b) an analyte molecule to which a tag is linked, (c) a tag, or (d) any combination thereof, to which an amplification element-linked recognition component is bound;
wherein the first recognition component has an affinity, capacity, or combination thereof for binding: (a) the analyte, (b) the analyte molecule to which the tag is linked, (c) the tag, or (d) any combination thereof, that is different from the affinity, capacity, or combination thereof for binding (a) the analyte, (b) the analyte molecule to which the tag is linked, (c) the tag, or (d) any combination thereof, of the second recognition component;
and
one or more containers housing an amplification element, a recognition component of the amplification element-linked recognition component, the tag, the analyte, or any combination thereof.
11. The kit of claim 10 , wherein the amplification element of the amplification element-linked recognition component is configured to contact an amplification precursor and convert the amplification precursor into a molecule that adds mass at the surface of the first BAW resonator sensor, the second BAW resonator sensor, or both.
12. The kit of claim 11 , wherein the amplification element comprises an enzyme and the amplification precursor comprises a substrate, and wherein the enzyme is configured to convert the substrate to a precipitate that adds mass at the surface of the first BAW resonator sensor, the second BAW resonator sensor, or both.
13. A method of increasing a dynamic range of a bulk acoustic wave (BAW) immunoassay, comprising:
contacting an analyte or an analyte molecule to which a tag is linked, a first recognition component, and an amplification element-linked recognition component to generate a complex comprising the first recognition component and the amplification element-linked recognition component,
wherein the first recognition component is immobilized relative to a surface of a first BAW resonator sensor and is configured to selectively bind: (a) the analyte, (b) the analyte molecule to which the tag is linked, (c) the tag, or (d) any combination thereof, to which the amplification element-linked recognition component is bound;
contacting an analyte or an analyte molecule to which a tag is linked, a second recognition component, and an amplification element-linked recognition component to generate a complex comprising the second recognition component and the amplification element-linked recognition component,
wherein the second recognition component is immobilized relative to a surface of a second BAW resonator sensor and is configured to selectively bind: (a) the analyte, (b) the analyte molecule to which the tag is linked, (c) the tag, or any combination thereof, to which the amplification element-linked recognition component is bound;
wherein the first recognition component has an affinity, capacity, or combination thereof for binding: (a) the analyte, (b) the analyte molecule to which the tag is linked, (c) the tag, or (d) any combination thereof, that is different from the affinity, capacity, or combination thereof for binding (a) the analyte, (b) the analyte molecule to which the tag is linked, (c) the tag, or (d) any combination thereof, of the second recognition component;
contacting an amplification element of the amplification element-linked recognition component with an amplification precursor under conditions to convert the amplification precursor into a molecule that adds mass at a surface of the first BAW resonator sensor, the second BAW resonator sensor, or both; and
measuring mass added at the surface of the first BAW resonator sensor, the second BAW resonator sensor, or both, thereby increasing the dynamic range of the BAW immunoassay.
14. The method of claim 13 , wherein the amplification element comprises an enzyme and the amplification precursor comprises a substrate, and wherein the enzyme is configured to convert the substrate to a precipitate that adds mass at the surface of the first BAW resonator sensor, the second BAW resonator sensor, or both.
15. The method of claim 13 , wherein the analyte or the analyte molecule to which the tag is linked are contacted with the amplification element-linked recognition component prior to contact with both the first and second recognition components immobilized relative to the surface of the first and second BAW resonator sensors, respectively.
16. The method of claim 15 , wherein the analyte or the analyte molecule to which the tag is linked are contacted with the first and second recognition components prior to contact with the amplification element-linked recognition component.
17. The method of claim 15 , wherein the analyte or the analyte molecule to which the tag is linked, the first recognition component, the second recognition component, and the amplification element-linked recognition component are contacted simultaneously.
18. The method of claim 13 , wherein the first and second recognition components are different.
19. The method of claim 18 , wherein the first recognition component has an affinity for binding: (a) the analyte, (b) the analyte molecule to which the tag is linked, (c) the tag, or (d) any combination thereof, that is lower than an affinity of the second recognition component for binding (a) the analyte, (b) the analyte molecule to which the tag is linked, (c) the tag, or (d) any combination thereof.
20. The method of claim 13 , wherein the first and second recognition components are the same and wherein the first recognition component has a concentration on the surface of the first BAW resonator sensor to which it is immobilized that is different from a concentration of the second recognition component on the surface of the second BAW resonator sensor to which it is immobilized.