Systems and methods for electronic detection with nanofets
There is disclosed a system for electrical charge detection comprising a nanoFET device. Also disclosed is a method of electrical charge detection for single molecule sequencing. The method includes attaching a macromolecule or assemblies thereof to a gate of a nanoFET device and flowing in a solution of charge tags, where a charge tag includes a nucleotide attached to a charge complex. The method also includes incorporating one charge tag into the macromolecule or assemblies thereof and cleaving the charge tags from the macromolecule or assemblies thereof. The method further includes detecting at least one of current and voltage from the nanoFET device.
1. A method of detecting a target protein, the method comprising:
attaching a first antibody to a surface of a device, the device having at least one nanoFET disposed in a well, the nanoFET having a source, a drain, and a gate, the first antibody disposed over the gate;
applying a sample including the target protein to the device, the first antibody having affinity for the target protein;
applying a plurality of types of additional antibodies, each type of additional antibody of the plurality of types of additional antibodies associated with a charge label having different charge than each other type of additional antibody of the plurality of types of additional antibodies, the plurality of types of antibodies including a second, the second antibody having affinity for the target protein, the target protein attaching to the first antibody and the second antibody attaching to the target protein to form an antibody assembly;
detecting with the nanoFET the presence of the antibody assembly; and
identifying the target protein based on a charge detected by the nanoFET and associated with the antibody assembly including the second antibody.
2. The method of claim 1 , wherein the target protein and the second antibody bind before the protein binds with the first antibody.
3. The method of claim 1 , wherein the target protein and the second antibody bind after the protein binds with the first antibody.
4. The method of claim 1 , wherein the device further includes two charge electrodes, the method further comprising applying a DC voltage to the charge electrodes to push the second antibody toward the nanoFET.
5. The method of claim 4 , wherein the DC voltage is in a range of 0.1 V/cm to 100 V/cm.
6. The method of claim 1 , wherein the device further includes two charge electrodes, the method further comprising applying a AC voltage to the charge electrodes to push the second antibody toward the nanoFET.
7. The method of claim 6 , further including applying a DC voltage with the AC voltage.
8. The method of claim 6 , wherein the AC voltage is in a range of 0.1 V/cm to 100 V/cm.
9. The method of claim 1 , wherein the plurality of types of additional antibodies includes a third antibody, the third antibody having a charge label different from the charge label of the second antibody.
10. The method of claim 1 , wherein the sample in the well includes another target protein, a third antibody of the plurality of types of additional antibodies having a charge label different from the charge label of the second antibody, the method further including detecting a second molecular assembly including the first antibody attached to the another target protein attached to the third antibody.
11. A method of detecting a target protein, the method comprising:
attaching antibodies to sensor surfaces of a device, the device having a plurality of nanoFETs, each nanoFET of the plurality of nanoFETs disposed in a separate well of a plurality of wells, each nanoFET having a source, a drain, and a gate, a sensor surface of the sensor surfaces disposed over the gate;
applying a sample including the target protein to the device;
applying a plurality of types of charge labeled antibodies to the device, each type of charge labeled antibody of the plurality of types of charge labeled antibodies having a different charge label, the target protein attaching to an antibody attached to the sensor surface and a charge labeled antibody of a type of charge labeled antibody of the plurality of types of charge labeled antibodies attaching to the target protein to form an antibody assembly;
detecting with the nanoFET a charge of the antibody assembly; and
identifying the target protein based on the charge of the antibody assembly.
12. The method of claim 11 , wherein the target protein and the charge labeled antibody bind before the protein binds with the antibody attached to the sensor surface.
13. The method of claim 11 , wherein the target protein and the charge labeled antibody bind after the protein binds with the antibody attached to the sensor surface.
14. The method of claim 11 , wherein the device further includes two charge electrodes, the method further comprising applying a DC voltage to the charge electrodes to push the charge labeled antibody toward the nanoFET.
15. The method of claim 14 , wherein the DC voltage is in a range of 0.1 V/cm to 100 V/cm.
16. The method of claim 11 , wherein the device further includes two charge electrodes, the method further comprising applying a AC voltage to the charge electrodes to push the charge labeled antibody toward the nanoFET.
17. The method of claim 16 , further including applying a DC voltage with the AC voltage.
18. The method of claim 16 , wherein the AC voltage is in a range of 0.1 V/cm to 100 V/cm.
19. The method of claim 11 , wherein the sample includes a second target protein, the second target protein attaching to a second charge labeled antibody of a second type of charge labeled antibody of the plurality of types of charge labeled antibodies, the second target protein binding to the antibody on a second sensor surface associated with a second nanoFET in a second well to form a second antibody assembly, the method further including detecting with the second nanoFET a second charge of the of the second charge assembly and identifying the second target protein based on the second charge of the second antibody assembly.