Apparatus for automatic sampling of biological species employing disk microfluidics system
Inventors
Shachar, Josh • Gurley, Sam • CIPRIANO, Aaron • Yin, Peter • Purnell, Rob • Rocklinger, Marc • Petrullo, Ming • Stelea, Stelica • PEREBIKOVSKY, Alexandra
Assignees
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Publication Number
US-12023674-B2
Publication Date
2024-07-02
Expiration Date
Abstract
A field portable diagnostic apparatus uses a rotatable disk in which a microfluidic circuit is defined. The microfluidic circuit includes a centrifugal separation chamber receiving a sample to stratify the sample. A magnetic bead holding chamber is communicated to a mixing chamber, where mass amplifying functionalized magnetic-nanoparticles, held in a buffer solution and contained in the magnetic bead holding reservoir communicated to mixing chamber, are mixed with the separated fluid delivered to mixing chamber from the separation chamber. The functionalized magnetic nanoparticles conjugate with a target analyte in the sample. A magnet in proximity to a SAW chamber including a SAW detector draws the functionalized magnetic nanoparticles toward antibodies immobilized on the SAW sensor surface A wash reservoir is communicated to the SAW sensor chamber, and a cleanup/waste reservoir is communicated to the SAW chamber for receive fluid after it has passed through the SAW chamber.
Core Innovation
The invention provides a field portable diagnostic apparatus with a microfluidic circuit defined in a rotatable disk having a center. The apparatus uses centrifugal separation on the rotatable disk to separate a sample, including separating blood into plasma via a plasma separation chamber. Separated components are transferred into a mixing chamber for downstream processing.
Functionalized magnetic nanoparticles are mixed with at least one separated component in the mixing chamber. Mixing is performed by spinning the rotatable disk using selectively reversed or oscillating cycles of rotation, including oscillating the rotatable disk at an oscillation angle of at least 180 degrees. The rotating and selectively controlled magnetic field interaction is used to magnetically retain and/or transfer conjugates associated with the functionalized magnetic nanoparticles.
The processed components are moved into at least one detection chamber by spinning the rotatable disk. The detection chamber comprises a shear horizontal surface acoustic wave (SH-SAW) biosensor for measuring at least one analyte, with notes on multiplexed SAW lanes including reference lanes for detection.
Claims Coverage
The provided material includes one independent claim directed to a method for operating a field portable diagnostic apparatus using a rotatable disk microfluidic circuit. The inventive features focus on centrifugal separation, oscillating/reversed rotation mixing with functionalized magnetic nanoparticles, transferring to an SH-SAW detection chamber, and measuring analytes using the SH-SAW biosensor; the dependent claims further refine this workflow with optional spin drying and constraints on oscillation angle and/or separation parameters.
Centrifugal separation in a rotatable disk for separating sample components
spinning the rotatable disk in the reader at a separation rate for a separation time to separate the sample into a plurality of separated components
Oscillating or reversed rotation mixing of functionalized magnetic nanoparticles in a mixing chamber
mixing functionalized magnetic nanoparticles with at least one of the plurality of separated components in a mixing chamber by spinning the rotatable disk using selectively reversed or oscillating cycles of rotation, where mixing functionalized magnetic nanoparticles with at least one of the plurality of separated component in a mixing chamber by spinning the rotatable disk comprises oscillating the rotatable disk at an oscillation angle of at least 180 degrees
Transfer to an SH-SAW biosensor detection chamber and analyte measurement
moving at least one of the plurality of separated components into at least one detection chamber by spinning the rotatable disk, the at least one detection chamber comprising a sheer horizontal surface acoustic wave (SH-SAW) biosensor; and measuring the at least one analyte in the at least one detection chamber comprising the SH-SAW biosensor
Spin drying of the SH-SAW detection chamber (optional refinement)
spin drying the detection chamber to remove fluid from an SH-SAW biosensor by spinning the rotatable disk
Magnetic-field immobilization and removal of unconjugated material (refinement)
immobilizes conjugated functionalized magnetic nanoparticles in a mixing chamber by applying a magnetic field, then removes unconjugated functionalized magnetic nanoparticles by spinning a rotatable disk while the magnetic field is maintained
PBS resuspension and oscillation-angle constrained transfer (refinement)
resuspending the conjugated functionalized magnetic nanoparticles in a PBS buffer and transferring them into at least one detection chamber by oscillating a rotatable disk at an oscillation angle of at least 180 degrees
Separation by first rotational speed for a first time period (parameter refinement)
carrying out the separation step by spinning a rotatable disk at a first rotational speed for a first time period
Measuring analyte using an SH-SAW biosensor without spinning the rotatable disk (operational refinement)
measuring the at least one analyte in at least one detection chamber using an SH-SAW biosensor without spinning a rotatable disk
Across the independent method and refinements described in the provided claim material, the main inventive coverage is the combination of rotatable-disk centrifugal separation with mixing in a mixing chamber using selectively reversed or oscillating rotation of a specified oscillation angle, followed by transfer into an SH-SAW biosensor detection chamber for analyte measurement, with optional spin-drying and refinements including magnetic-field-based immobilization/removal and PBS resuspension.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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