Honeycomb tube
Inventors
Chiang, Yuh-Min • DORITY, DOUG • DICKENS, DUSTIN • GLASS, JENNIFER • Van Atta, Reuel
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Assignees
Member
CepheidCepheid is a global leader in molecular diagnostics, dedicated to improving healthcare by developing, manufacturing, and marketing automated, easy-to-use molecular systems and tests. Their mission is to provide rapid, accurate, and actionable genetic testing for a wide range of infectious diseases, oncology, and human genetics. Cepheid's flagship GeneXpert System delivers scalable, sample-to-answer PCR testing for institutions of any size, supporting both centralized and decentralized care. The company is committed to expanding access to high-quality diagnostics worldwide, supporting public health initiatives, driving innovation in molecular testing, and advancing sustainability and responsible business practices.
Cepheid is a global leader in molecular diagnostics, dedicated to improving healthcare by developing, manufacturing, and marketing automated, easy-to-use molecular systems and tests. Their mission is to provide rapid, accurate, and actionable genetic testing for a wide range of infectious diseases, oncology, and human genetics. Cepheid's flagship GeneXpert System delivers scalable, sample-to-answer PCR testing for institutions of any size, supporting both centralized and decentralized care. The company is committed to expanding access to high-quality diagnostics worldwide, supporting public health initiatives, driving innovation in molecular testing, and advancing sustainability and responsible business practices.
Publication Number
US-12281358-B2
Publication Date
2025-04-22
Expiration Date
Abstract
A honeycomb tube with a planar frame defining a fluidic path between a first planar surface and a second planar surface. A fluidic interface is located at one end of the planar frame. The fluidic interface has a fluidic inlet and fluidic outlet. The fluidic path further includes a well chamber having an well-substrate with a plurality of wells. The well chamber is arranged in the planar frame between the first or second surface and the well-substrate.
Core Innovation
Some embodiments of the invention relate to a honeycomb tube having a planar frame defining a fluidic path between a first planar surface and a second planar surface, where a fluidic interface is located at one end of the planar frame and the fluidic interface has a fluidic inlet and a fluidic outlet. The fluidic path can include a well chamber having a well-substrate configured with a plurality of wells, the well chamber being arranged in the planar frame between the first or second surface and the well-substrate, the well chamber being in fluidic communication with the fluidic inlet and the fluidic outlet. In some embodiments the fluidic path can include a pre-amplification chamber arranged in the planar frame between the first and second planar surfaces and the well chamber can be positioned between the pre-amplification chamber and the fluidic outlet.
The background describes a need for devices that can perform multiplexing assays to perform a plurality of assays simultaneously to provide varied and large data sets. The honeycomb tube embodiments address that need by providing a multi-well reaction chamber (well chamber or well-substrate) and associated fluidic path and interfaces to enable filling, isolation (for example with oil), thermal cycling, and optical monitoring for multiplex amplification and detection assays.
Claims Coverage
The independent claims recite inventive features across two independent method claims and together disclose seven main inventive features related to reaction vessel structure, fluidic interface and path, sample introduction by pressurized flow, filling of a well array, evacuation leaving sample in wells, and optional post-filling hydrophobic fluid introduction and serpentine channel geometry.
Planar reaction vessel with fluidic interface
A reaction vessel comprising a planar frame elongated length-wise between opposite ends with a fluidic interface at one end having a fluidic inlet and a fluidic outlet, and a fluidic path extending between the fluidic inlet and the fluidic outlet, the well chamber being disposed along the fluidic path and having a plurality of wells defining the well array.
Introducing liquid sample by pressurized fluid flow
Introducing the liquid sample, by pressurized fluid flow, through the fluidic inlet of the fluidic interface of the reaction vessel and advancing the liquid sample along the fluidic path.
Depositing liquid sample within plurality of wells by advancing sample
Filling the well chamber along the fluidic path with the liquid sample by further advancing the liquid sample along the fluidic path thereby depositing the liquid sample within the plurality of wells of the well chamber.
Evacuating fluid while retaining liquid in wells
Evacuating at least a portion of the liquid sample from the well chamber outside of the plurality of wells via application of pressure to the fluidic interface such that at least some of the liquid sample remains deposited within the plurality of wells of the well array.
Body elongated reaction vessel embodiment
A method of filling a plurality of wells in a reaction vessel comprising a body elongated between opposite ends and having a fluidic interface at one end, the fluidic path extending length-wise between the fluidic inlet and the fluidic outlet, the well chamber being disposed along the fluidic path and having a plurality of wells defining the well array.
Post-evacuation hydrophobic fluid filling
Filling the well chamber with a hydrophobic fluid substance after evacuating at least a portion of the liquid sample from the well chamber outside of the plurality of wells, wherein the hydrophobic fluid substance can be an oil supplied from an oil chamber of the planar frame that is fluidically connected with the well chamber.
Serpentine channel and pressure control features
A fluidic path that can include a serpentine channel portion between the fluidic inlet and the well chamber and application of pressure comprising applying a positive or negative pressure via the fluidic inlet or the fluidic outlet to introduce, advance, or evacuate fluid.
The independent claims cover methods and apparatus features for a planar elongated reaction vessel with a fluidic interface and internal fluidic path, pressurized introduction and advancement of a liquid sample to deposit sample into a plurality of wells, evacuation to leave sample retained in wells, optional introduction of a hydrophobic fluid (such as oil) after evacuation, and fluidic path geometries and pressure-control means to effect these steps.
Stated Advantages
Enables performance of a plurality of assays simultaneously (multiplexing assays) to provide varied and large data sets.
Torturous or serpentine channel geometry can help reduce formation of gas bubbles that can interfere with flowing oil through the fluidic path.
Cone-shaped (tapered) wells offer an advantage during primer application by enabling non-contact deposition methods and aiding in drying, and help prevent bubbles and leaks when a gas permeable membrane is present.
An oil cap or other thermally conductive liquid can isolate each well to reduce evaporation during thermal cycling and provide thermal conductivity.
A gas permeable membrane enables gas to be evacuated from the wells while not allowing fluid to pass through.
Surface treatments (hydrophilic well surfaces and hydrophobic surrounding surfaces) encourage retention of fluid within wells while discouraging retention on upper surfaces to reduce inconsistent testing results and cross-contamination.
Sharply angled interior curves with reduced cross-sectional area around corners help reduce flow rate differentials and prevent cavitation and bubble formation.
Conductive metal portions of the well-substrate can enable heat transfer from the metal to the wells.
Documented Applications
Performing multiplex amplification reactions in the honeycomb tube, including nested PCR and multiplexed PCR.
Real-time monitoring of amplification reactions using fluorescent indicators and melt-curve analysis.
Detection of presence or absence of single nucleotide polymorphisms (SNPs).
Detection of the presence or absence of proteins using binding affinity-based assays such as sandwich immunoassays.
Detection and/or quantitation of nucleic acids including DNA, mRNA, and microRNA using amplification-based assays such as PCR and RT-PCR.
Use in diagnostic detection of viral, bacterial, fungal, parasitic, animal, or human analytes including specific viruses, bacteria, and human genes enumerated in the specification.
Loading wells with pre-deposited analytic probes or dried reagents (e.g., primer sets) for later rehydration and assay.
Integration with a fluid control and processing cartridge to provide sample fluid and other fluids via the fluidic interface, for example in a GeneXpert® system.
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