Methods for increasing the molecular specificity of a nanosensor
Inventors
Erramilli, Shyamsunder • Mohanty, Pritiraj
Assignees
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Abstract
Systems and methods for detecting a target species using a semiconductor nanosensor are generally described.
Core Innovation
The disclosed subject matter provides systems and methods to improve molecular specificity and sensitivity of semiconductor nanosensors, including a silicon nanochannel/FET nanosensor. A molecular binding event is associated with a surface of a semiconductor nanosensor, and an amplification agent is associated with a first species capable of participating in the molecular binding event with that surface. The amplification agent is further associated with at least three binding agents via binding sites on the amplification agent.
The binding agents comprise nanoparticles, and the amplification agent associates these nanoparticles with the molecular binding event occurring at the semiconductor nanosensor surface. In this way, the approach increases the nanosensor signal-to-noise ratio compared with similar conditions without the associating/releasing step. The document describes architectures such as sandwich and indirect ELISA using enzyme amplification such as HRP, including nanoparticle binding-agent enhancement.
The document also describes assay architectures that include releasable-agent displacement to reduce noise, and it identifies selection of functionalizing biomolecules including antibodies, aptamers, and nucleic acids. Debye-length proximity constraints are described for operating conditions involving molecular binding near the sensor surface. Example testing includes cardiac troponin I detection using HRP-tagged sandwich ELISA on silicon nanowire nanosensors, with reported conductance versus time and concentration dependence relationships.
Claims Coverage
Only one independent claim is provided. It covers a method that includes associating an amplification agent with a first species that participates in a molecular binding event on a semiconductor nanosensor surface, where the amplification agent is associated with at least three nanoparticle binding agents via binding sites.
Associating amplification agent with first species on semiconductor nanosensor surface
Associating an amplification agent with a first species capable of participating in a molecular binding event that is associated with a surface of a semiconductor nanosensor.
Amplification agent with at least three nanoparticle binding agents via binding sites
Associating the amplification agent with at least three binding agents via binding sites on the amplification agent, wherein the binding agents comprise nanoparticles.
The provided independent claim requires an amplification agent linked to a first species involved in a molecular binding event at the semiconductor nanosensor surface, where the amplification agent binds at least three nanoparticle binding agents through binding sites.
Stated Advantages
Improves molecular specificity and sensitivity of semiconductor (silicon nanochannel/FET) nanosensors.
Increases the nanosensor signal-to-noise ratio versus similar conditions without the associating/releasing step (at least 2×, potentially much higher).
Reduces noise using releasable-agent displacement in assay architectures.
Documented Applications
Cardiac troponin I detection using HRP-tagged sandwich ELISA on silicon nanowire nanosensors.
Detection/assay architectures involving sandwich ELISA and indirect ELISA with enzyme amplification such as HRP and nanoparticle binding-agent enhancement.
Use of functionalizing biomolecules including antibodies, aptamers, and nucleic acids as binding agents in molecular binding events on semiconductor nanosensors.
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