Nanowires are microscopic electric wires whose diameter can be as small as 10 nanometers or less. A Field Effect Transistor (FET) is a tiny "switch" with two circuits, one with a small current flow (the gate), and the other with a much greater flow. Electrical current changes in the gate produce concomitant, amplified current changes in the more powerful detector circuit. At Vista, functionalized nanowires serve as the gates that allow detection of target molecules at the level of tens of proteins per ml. The number of markers measured is limited only by the number of nanowire circuits that can be placed in a microfluidics chip.

Biomarker Detection is possible because ‘capture’ molecules such as antibodies or oligonucleotide probes can be covalently attached to each nanowire. By adjusting the pH of the sample fluid, target molecules become charged. Binding of charged target to complementary capture molecules changes the electric field near the nanowire and are thus sensitively detected.

Conductance of the nanowire is affected by the number of charged target molecules (proteins, oligonucleotides, drugs or drug candidates), and the total number of charges per molecule specifically bound to the capture molecule on the nanowire surface. Binding increases or decreases across time depending on the concentration of the target molecule in the sample fluid. The conductance can be monitored, with a high degree of sensitivity, in real time, without labels. Vista is working to allow simultaneous detection of gene transcripts and proteins.

The above micro-photo actually shows a single virus binding (and unbinding) from a nanowire during experimentation.

Through a process like the one shown to the right, nanowires can be functionalized for detection of many molecules-of-interest, including antibodies, oligonucleotides, enzymes, and small molecules. Conductance through a nanowire FET is directly related to the number of attached antibodies that are bound to the target biomarker. The proportion of bound versus free antibodies is directly related to the concentration of target molecules in the sample.

Nanowire serves as FET gate

Functionalizing a Nanowire
for Antigen Detection