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How Vista's silicon nanowire FETs detect biomarkers

At the heart of Vista's NanoBioSensor are silicon nanowires. At 30-50 nm in diameter, they are far smaller than red blood cells and approach the size scale of proteins, nucleic acids and virions. By doping for n-type or p-type characteristics as they are grown, they act as nanoscale Field Effect Transistors (FETs). As the name implies, these are transistors that respond to electric fields. This means that electric fields in the vicinity of the nanowire sidewall change the conductance of the nanowire channel between its ends in proportion to the magnitude of the electric field in a predictable way. When wired into a circuit, the ends are known as the source (S) and drain (D), while the sidewall is called the gate. The SEM image at the center left shows detail of a completed nanowire circuit on a Vista NanoCard chip. The electrodes S and D are labeled with a 2 micron gap which the nanowire bridges. We'll next discuss how functionalizing the sidewall of the nanowire with capture molecules to a biomarker creates a powerful biomarker detection tool.

Specificity and sensitivity

Biomarkers such as viruses, soluble serum proteins and nucleic acids are soluble because they carry formal charges at physiological pH (e.g. TNF-alpha has about 20 negative charges at pH 8.4. The Zika virus has thousands). The definition of an electric field at a point is the linear superposition of charges as the inverse square of their distance. By functionalizing the the nanowire with a capture molecule (e.g. mABs, aptamers or nanobodies) the nanowire's sensitivity is then combined with great specificity. Due to the E-field inverse square law with distance and charge screening in solution, only those charged biomarkers bound to the capture molecules contribute a meaningful electric field to gate the nanowire. This means not only is the biomarker detected, but its concentration is also known due to the predictable change in nanowire channel conductance with the magnitude of the gating electric field.

How sensitive?

The graphic above shows just how sensitive Vista's silicon nanowire FET based NanoBioSensorTM is relative to the gold standard ELISA. The depicted comparison is prostate specific antigen (PSA). Not only is our nanowire sensing more sensitive, it has 5 logs of dynamic range vs. ELISA's 2 to 2.5. Depending on the biomarker, our sensitivity is typically femtograms/mL in such media as dilute capillary blood, urine or buffer and single virions in 1 mL capillary blood.

Dynamic or snapshot

While the NanoBioSensorTM will give you a snapshot of the instantaneous concentration of your biomarker in seconds or minutes by dipping into your sample or pipetting onto a NanoCard, the real power is watching dynamically unfolding events. The binding constant of your capture molecule sets an expectation time for duration of the binding event. Capture molecules we typically use have a binding time of approximately seven seconds. Since biomarkers are continually binding and unbinding, an equilibrium is established of the number of bound biomarkers at any given instant for a particular concentration. This both gives the opportunity to measure the kinetics of the binding event for a change in concentration and watch dynamic changes as they unfold, be it in an in vitro experiment or by IV venous monitor of your research subject.

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Vista Therapeutics, Inc.
3900 Paseo del Sol
Santa Fe, NM 87507
Phone: 1-505-474-3143
Fax: 1-505-424-1144
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