FET Sensors With Subtractive Probes for Indirect Detection and Methods

A field effect transistor (FET) biosensor, comprising:

• a) a field effect transistor having a FET gate dielectric surface;
• b) a linker probe attached to said FET gate dielectric surface;
• wherein said linker probe comprises:
• i) a conformation changing region capable of changing three dimensional shape in the presence of a target entity;
• ii) an aptamer region attached to said conformation changing region, said aptamer region capable of selectively binding a target entity;
• wherein binding of said target entity to said aptamer region results in a conformational change of said conformation changing region, thereby inducing a measurable change in an electrical parameter of said FET.

A method of indirectly detecting the presence of or concentration of a target molecule with a FET sensor, comprising the steps of:

• taking a first measurement of an electrical parameter of an FET to determine a baseline of said electrical parameter, said FET comprising
• a) a field effect transistor having a FET gate dielectric surface;
• b) a linker probe attached to said FET gate dielectric surface;
• wherein said linker probe comprises:
• i) an enzymatic region capable of cleaving nucleic acids having a predetermined nucleic acid sequence, and
• ii) an aptamer region attached to said enzymatic region, said aptamer region capable of selectively binding a target entity;
• placing a solution having an unknown quantity of said target entity in contact with said linker probe on said gate dielectric surface;
• taking a second measurement of said electrical parameter with said FET;
• and
• determining the presence or concentration of said target molecule by comparing said first measurement of said electrical parameter with said second measurement of said electrical parameter,
• whereby if said first measurement is different from said second measurement by a threshold value, said target molecule is determined to be present in the said solution;
• and,
• whereby the greater the difference between said first measurement and said second measurement of said electrical parameter, the higher the concentration of said target molecule in the solution.