Integrated apparatus for performing nucleic acid extraction and diagnostic testing on multiple biological samples
Inventors
Williams, Jeff • Wilson, Kerry • Handique, Kalyan
Assignees
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Publication Number
US-11845081-B2
Publication Date
2023-12-19
Expiration Date
Abstract
The technology described herein generally relates to systems for extracting polynucleotides from multiple samples, particularly from biological samples, and additionally to systems that subsequently amplify and detect the extracted polynucleotides. The technology more particularly relates to microfluidic systems that carry out PCR on multiple samples of nucleotides of interest within microfluidic channels, and detect those nucleotides.
Core Innovation
The invention is an integrated diagnostic system that includes a liquid dispenser with a plurality of dispense heads, pipette tips, and one or more valves that vary pressure by controlling flow of gas through the valves, so that fluid is drawn up into or expelled from a pipette tip attached to a respective dispense head. The system further includes a stripper plate comprising a defined hole structure configured to move relative to the pipette tip to detach the pipette tip from the respective dispense head.
Sample identification is performed with a sample tube holder having a first rack portion for an upper portion of a sample tube and a second rack portion for a lower portion, with a middle portion of the sample tube between the upper and lower portions visible when received in the sample tube holder. A mirror is positioned relative to the sample tube holder, and a barcode scanner reads a barcode disposed on the middle portion of the sample tube through a non-linear field of view to the mirror and the middle portion, enabling detection of light reflected by the mirror from the sample tube.
The system also includes an integrated diagnostic apparatus with a preparatory module and a diagnostic module that perform parallel nucleic-acid extraction and real-time PCR detection. Disposable reagent holders or strips include process tubes and reagent receptacles, including lyophilized reagents sealed for storage, along with waste chambers, and the diagnostic module uses disposable multi-lane microfluidic cartridges with inlet valves, PCR reaction chambers, optical windows for fluorescence detection, and an autoloader or stacker to feed cartridges to a receiving bay with contact heating and fluorescence read-head optics for multi-color detection.
Claims Coverage
Independent claim coverage centers on three inventive features: a gas-valve-controlled liquid dispenser with pipette tips, a sample tube holder with mirror-based non-linear barcode scanning, and a stripper plate with a defined hole structure for detaching pipette tips. Additional claim language in the inputs also refers to processor-based association of barcode identity to diagnostic results and additional operational details.
Gas-valve-controlled pressure dispense from multiple dispense heads using pipette tips
A liquid dispenser comprising a plurality of dispense heads each configured to accept a pipette tip from a holder; one or more valves; and wherein by controlling flow of gas through the one or more valves, pressure above the plurality of dispense heads is configured to be varied so that fluid is drawn up into or expelled from a pipette tip attached to a respective dispense head.
Mirror-based non-linear barcode scanning using a visible middle portion of a sample tube
A sample tube holder comprising a first rack portion configured to be disposed around an upper portion of a sample tube and a second rack portion configured to be disposed around a lower portion of the sample tube, wherein a middle portion of the sample tube between the upper portion and the lower portion is visible when the sample tube is received in the sample tube holder; a mirror positioned relative to the sample tube holder; and a barcode scanner configured to read a barcode disposed on the middle portion of the sample tube, wherein the barcode scanner has a non-linear field of view from the barcode scanner to the mirror to the middle portion of the sample tube, enabling the barcode scanner to detect light reflected by the mirror from the sample tube.
Stripper plate with defined hole structure moved relative to the pipette tip for tip detachment
A stripper plate comprising a defined hole structure, configured to move relative to the pipette tip to detach the pipette tip from the respective dispense head.
The claim coverage is directed to a diagnostic system that couples gas-valve-controlled pressure variation for pipette-tip aspiration and dispense, mirror-based barcode reading from a visible middle portion of a sample tube, and a defined-hole stripper plate that moves relative to the pipette tip to detach it.
Stated Advantages
High automation.
Rapid time-to-result.
Low-volume sensitive fluorescence readout.
Simplified reagent logistics.
Reduced contamination risks in diagnostic workflows.
Documented Applications
Automated microfluidic PCR diagnostic operation using neutralized polynucleotide sample processing, probe-based detection, positive and negative controls, and determination/contamination logic with multiplexed fluorescence detection.
Parallel nucleic-acid extraction and real-time PCR detection performed by a self-contained diagnostic system using a two-mode preparatory/diagnostic platform.
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