Diagnostic and sample preparation devices and methods
Inventors
Kelley, Shana O. • Bortolin, Susan • Orton, Reginald James McKenzie • Wiechula, Stefan Christopher
Assignees
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Publication Number
US-10301666-B2
Publication Date
2019-05-28
Expiration Date
Abstract
Contemplated methods and devices are drawn to preparation and analysis of analytes from biological samples. In a preferred embodiment the analytes are nucleic acids that are both released from biological compartments present in the sample and fragmented through the use of a voltage potential applied to a pair of electrodes. The nucleic acids thus prepared are subsequently characterized.
Core Innovation
The invention relates to a device for analyzing a biological sample that includes nucleic acids by using an electrically driven sample extraction zone. The device includes a sample receiving zone configured to receive the biological sample and a sample extraction zone in fluid communication with the sample receiving zone, where the sample extraction zone includes a plurality of electrodes in electrical communication with an electrical source and configured to fragment the nucleic acids into fragmented nucleic acids when a first electrical signal is applied to the plurality of electrodes.
The device further includes a signal control unit that determines an overall treatment time of the first electrical signal applied to the plurality of electrodes based on a desired average length in bases of the fragmented nucleic acids. The overall treatment time is selected to control the desired fragment length, thereby producing fragmented nucleic acids for downstream analysis. After extraction and fragmentation, the device includes a sample analysis zone in fluid communication with the sample extraction zone.
The sample analysis zone includes a sensing electrode and a reference electrode for analyzing the biological sample. In described embodiments, the sensing electrode can include a probe molecule at least partially complementary to the fragmented nucleic acid, and the sensing electrode can include a nanostructured microelectrode that is at least one of textured or fractal. The disclosed architectures include sample receiving and extraction zones and analysis zones arranged within a cartridge or sample-to-answer device, with integration into microfluidic devices described in the document.
Claims Coverage
The independent claims cover 3 core inventive features, with dependent claims adding fluid handling, electrode geometry, extraction/release-fragmentation, and sensing electrode structure.
Electrode-driven nucleic-acid fragmentation in an extraction zone
A sample extraction zone in fluid communication with the sample receiving zone, including a plurality of electrodes in electrical communication with an electrical source and configured to fragment the nucleic acids into a plurality of fragmented nucleic acids when a first electrical signal is applied to the plurality of electrodes.
Treatment-time determination based on desired fragment length
A signal control unit configured to determine an overall treatment time of the first electrical signal applied to the plurality of electrodes based on a desired average length in bases of the plurality of fragmented nucleic acids.
Electrochemical analysis using sensing and reference electrodes
A sample analysis zone in fluid communication with the sample extraction zone and including a sensing electrode and a reference electrode for analyzing the biological sample.
Pressure-driven flow via a pliant-wall reservoir
A fluid reservoir with a pliant wall that deforms when external pressure is applied, thereby driving fluid flow through a sample receiving zone.
Electrode ridges or projections extending into a flow channel
A flow channel with multiple electrodes along the channel length, where the electrodes have ridges or projections extending into the flow channel.
Extraction-zone electrodes configured to release and fragment nucleic acids
Multiple electrodes positioned in an extraction zone that releases nucleic acids from a biological sample and fragments the nucleic acids.
Complementary probe molecule on the sensing electrode
A sensing electrode whose probe molecule is at least partially complementary to the fragmented nucleic acid.
Nanostructured microelectrode for the sensing electrode
A sensing electrode that includes a nanostructured microelectrode that is at least one of textured or fractal.
Overall, the claims cover a device that receives nucleic-acid-containing biological samples, fragments the nucleic acids in an extraction zone using a plurality of electrodes driven by a first electrical signal, and controls an overall treatment time to obtain a desired average fragment length, followed by analysis using a sensing electrode and a reference electrode. Dependent claim features further specify fluid driving with a pliant-wall reservoir, electrode geometry with ridges or projections, extraction-zone release coupled to fragmentation, and sensing electrode features including complementary probe molecules and nanostructured textured or fractal microelectrodes.
Stated Advantages
The document describes reduction of hybridization/analysis time by producing fragmented nucleic acids with smaller lengths.
Documented Applications
Point-of-care analysis using a cartridge/sample-to-answer device and analysis integration into microfluidic devices.
Analyzing biological samples containing RNA, with described time-dependent RNA release and fragmentation results.
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