Multi-chambered assay devices and associated methods, systems and apparatuses thereof for detection of analytes
Inventors
Simpson, Miriam Cather • VARGAS, Matheus Jose Teixeira • CHANDRASEKHAR, Mithileshwari • Williams, David Edward
Assignees
Publication Number
US-11565260-B2
Publication Date
2023-01-31
Expiration Date
2041-03-22
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Abstract
Accordingly, in some embodiments of the disclosure, a multi-chambered assay device is provided, which is configured for arrangement on a disc, as well as configured to process an individual sample. A plurality of such assay devices can be arranged along a periphery of the disc at a distance/radius from the center, such that a plurality of individual samples can be processed, e.g., one per assay device. In addition, in an arrangement that a plurality of assay devices are used, they can be spaced apart such that they balance the disc during rotation (which can be with samples contained in one or more of the assay devices, a plurality, a majority, or all of the assay devices).
Core Innovation
The invention provides multi-chambered assay devices configured for use on a disc, designed to process individual biological samples rapidly and with high precision. These assay devices include multiple chambers such as peripheral chambers for receiving fluids, a resuspension chamber with a scaffold for drying and retaining reagents, a main chamber containing at least one functionalized bead for capturing analytes, and a bead stabilization area. The assay devices are arranged along the periphery of a rotating disc in a spaced apart manner to balance centrifugal forces and enable simultaneous processing of multiple samples.
The assay devices operate within a centrifugal microfluidic system that controls motion by varying rotational speeds, direction changes, and acceleration/deceleration of the disc. Fluid and reagent mixing, transfer between chambers, resuspension of dried reagents, and fluid flow are precisely managed by microfluidic capillary valves, siphons, and disc rotation dynamics. The design facilitates rapid and uniform mixing, enhances contact between reagents and capture surfaces, and enables automated immunoassays suitable for minimally trained operators.
The problem addressed by the invention is the limitations of classical surface-binding immunoassays, which are slow, require skilled operators, and have long assay times. Rapid assay tests offer speed but lack precision and quantitative accuracy. Microfluidic and centrifugal systems face challenges in achieving rapid mixing and reagent resuspension essential for precise, rapid assays. This invention aims to provide an automated, rapid, and precise disc-based immunoassay platform that overcomes these issues by integrating multi-chamber assay devices with controlled fluid dynamics and reagent handling.
Additional embodiments include vial-based assay systems and methods, microfluidic pneumatic centrifuge mixing systems that utilize pneumatic pressure changes during disc spinning for enhanced fluid mixing, and fluid height control microfluidic chips to maintain consistent fluid levels enhancing measurement reproducibility. These components collectively address key challenges in immunoassay automation, speed, precision, and usability.
Claims Coverage
The patent claims seven main inventive features centered on a multi-chamber assay device configured for disc-based immunoassays, emphasizing fluid handling, reagent resuspension, and bead stabilization.
Multi-chamber assay device configured for disc arrangement and individual sample processing
An assay device arranged on a disc periphery with multiple chambers for fluid input, a resuspension chamber containing a scaffold to dry and retain reagents, a main chamber with a mixing area, at least one bead, and a separate bead stabilization area sized and fluidically connected to capture beads outside the mixing area.
Peripheral chambers with associated inlet areas and microchannels
At least first, second, and third peripheral chambers each having a corresponding inlet area in fluid communication via dedicated microchannels allowing controlled fluid transfer into each peripheral chamber.
Resuspension chamber with mesh scaffold for reagent retention and flow communication
A resuspension chamber including a mesh scaffold, configured as a geometric shape (e.g., circular disc 1-6 mm diameter) with specific mesh pore sizes, in fluid communication with at least one peripheral chamber via microfluidic channels to facilitate reagent drying and resuspension.
Main chamber design with mixing area and detection window
A main chamber including a mixing area arranged distal toward the disc edge, optionally with pre-stored reagents, configured to receive fluids from peripheral chambers and comprising a detection window; further including a bead stabilization area for holding beads during measurement.
Functionalized bead with capture reagents and dimensional specifications
At least one bead present in the main chamber bearing capture reagents such as antibodies or antigens covering a surface portion, with bead diameter between 100 μm and 2500 μm.
Siphon channels with microfluidic capillary valves for reagent timing and fluid transfer
First and second siphon channels each equipped with microfluidic capillary valves, configured with size and length to provide timed mixing and transfer of dried reagent resuspension fluid and main chamber fluid flow communication, including pressure release capillary valves and waste chamber connectivity.
Microfluidic capillary valves with hydrophobic surface modification
Capillary valves comprising dried hydrophobic material to decrease wettability in specific areas to control fluid flow based on disc rotational speed, including surface contact angle modification to prevent uncontrolled fluid bridging and require pressure increase to open the valve.
The claims cover a sophisticated multi-chamber assay device integrating microfluidic structures, reagent scaffolding, bead stabilization, and hydrodynamically controlled fluid transfer mechanisms on a disc platform, enabling precise, automated immunoassays through controlled centrifugal forces and fluidic valving.
Stated Advantages
Provides a rapid and precise immunoassay platform capable of processing multiple samples simultaneously with short total assay times.
Enables automated assays suitable for minimally trained operators by integrating reagent drying and rapid resuspension within the assay device.
Improves mixing speed and uniformity through controlled rotational dynamics including acceleration, deceleration, and oscillatory rotation of the disc.
Balances centrifugal forces on the disc by spacing assay devices along the periphery, ensuring stable rotation.
Enhances the accuracy and repeatability of assays by precise fluid control via microfluidic capillary valves with surface modifications.
Facilitates measurement by stabilizing functionalized beads in a dedicated chamber area for optical detection.
Improves sensitivity by using pneumatic pressure-assisted fluid mixing during centrifugation.
Provides fluid height control to maintain reproducible fluid levels for improved spectroscopic measurements.
Documented Applications
Automated disc-based immunoassays for rapid and precise detection of analytes such as proteins or antibodies in biological samples.
High-throughput sample processing scenarios such as airport entry gates requiring timely decisions on access or quarantine.
Vial-based assay kits for immunoassay with functionalized beads enabling competitive binding, washing, and colorimetric detection.
Centrifugal microfluidic systems incorporating pneumatic mixing methods to enhance fluid mixing within reaction chambers.
Microfluidic fluid levelling chips to improve reproducibility in vibrational spectroscopy and Raman spectroscopy of liquids.
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