Bionanosensor detection device

Inventors

Sinha, Saion KumarSapi, Eva Terezia

Assignees

12 15 Molecular Diagnostics Inc

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Publication Number

US-9919922-B2

Patent

Publication Date

2018-03-20

Expiration Date


Abstract

The present invention is directed to a nucleic acid detection device and method that incorporates bio-nanosensor technology to detect duplex DNA. The device is particularly applicable in detecting the presence or absence of duplex DNA and its correlation to the diagnosis of infectious diseases. In one embodiment, the infectious disease is Lyme disease or a bacterial or viral infection. The device comprises a bio-nanosensor element comprising ssDNA primed nanotubes, either single walled or multi-walled. The method comprises contacting the bio-nanosensor element with a test solution potentially containing DNA of interest. DNA of interest that hybridizes to the ssDNA results in a measurable change in the electrical properties of the bio-nanosensor. Correlations between the results provided by the device and the presence of disease states can result in rapid diagnosis of diseases such as Lyme disease or foodborne infections such as salmonellosis.

Core Innovation

The invention provides a bio-nanosensor detection device that includes a bio-nanosensor element with a plurality of carbon nanotubes coated with single stranded pathogen-specific nucleic acids. The carbon nanotubes are precoated with a binding agent prior to operation, and each nanotube has at least a pair of ends electrically coupled to a substrate formed from printed circuit board material. The device further includes an electrical monitoring device that uses a 4-point probe with a first electrode and second electrode positioned on ends of the substrate.

The electrical monitoring device is configured so the first electrode and second electrode are in electrical communication through the carbon nanotubes without passing electrical current directly through the single stranded pathogen-specific nucleic acids. The first electrode and second electrode are in electrical communication with a current source, and the monitoring device includes a first voltage terminal and a second voltage terminal in electrical communication with the carbon nanotubes and a signal indicator. The device provides an unamplified signal to the signal indicator and produces detection based on electrical response.

The electrical monitoring device includes an LED indicator that indicates a change in resistance between the electrodes of the bio-nanosensor element without electrical amplification in response to non-PCR based hybridization between the single stranded pathogen-specific nucleic acid and a complementary nucleic acid in a sample. The resulting resistance change is used to detect the presence of a pathogen on the bio-nanosensor element.

Claims Coverage

The independent claim defines a complete bio-nanosensor detection device and its electrical monitoring architecture. It includes three inventive features that collectively enable unamplified, non-PCR based nucleic-acid hybridization detection using resistance change indicated by an LED, with electrical monitoring implemented by a 4-point probe.

Carbon nanotubes precoated with binding agent and single stranded pathogen-specific nucleic acids

A bio-nanosensor element comprising a plurality of carbon nanotubes coated with single stranded pathogen-specific nucleic acids, wherein the carbon nanotubes are precoated with a binding agent prior to operation, and each nanotube has at least a pair of ends electrically coupled to a substrate formed from printed circuit board material.

4-point probe electrical monitoring without current through nucleic acids

An electrical monitoring device comprising a 4-point probe with a first electrode and second electrode positioned on ends of the substrate, wherein the first electrode and second electrode are in electrical communication through the carbon nanotubes without passing electrical current directly through the single stranded pathogen-specific nucleic acids, and are in electrical communication with a current source.

Unamplified LED resistance-indicator for non-PCR hybridization

A first voltage terminal and a second voltage terminal in electrical communication with the carbon nanotubes and a signal indicator, wherein the electrical monitoring device provides an unamplified signal and includes an LED indicator that indicates a change in resistance between the electrodes without electrical amplification in response to non-PCR based hybridization between the single stranded pathogen-specific nucleic acid and a complementary nucleic acid in a sample to detect the presence of a pathogen on the bio-nanosensor element.

Overall claim coverage is centered on a carbon-nanotube bio-nanosensor element with single stranded pathogen-specific nucleic-acid probes and precoated binding agent, paired with 4-point probe electrical monitoring that prevents direct current through the nucleic acids and produces an unamplified, non-PCR hybridization-dependent resistance change indicated by an LED.

Stated Advantages

Detects the presence of a pathogen on the bio-nanosensor element based on non-PCR based hybridization.

Indicates a change in resistance between electrodes without electrical amplification.

Provides an unamplified signal to the signal indicator.

Uses an LED indicator to indicate the resistance change.

Documented Applications

Infectious disease detection, including tick-borne infections and foodborne infections, using pathogen-specific nucleic acids (as described for Borrelia burgdorferi and Salmonella enterica).

Detection and quantification in a portable, point-of-care context, with operation discussed for clinical, field, and food samples in the partial content.

Duplex DNA detection is referenced via hybridization-specific detection based on measurable electrical property changes.

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