Microfluidic device for whole blood sample preparation
Inventors
Assignees
University of California San Diego UCSD • University of California Irvine
Publication Number
US-9186672-B2
Publication Date
2015-11-17
Expiration Date
2032-04-17
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Abstract
A CD-based device for separating plasma from whole blood includes a substrate, a sedimentation chamber disposed in the substrate, and a collection chamber disposed in the substrate and in fluidic communication with the sedimentation chamber through a siphon channel. The sedimentation chamber includes a plurality of finger-like structures disposed along a radially outward edge of the sedimentation chamber, and protruding radially inward relative to the axis of rotation of the substrate. A method for separating plasma from whole blood using the CD-based device includes introducing a blood sample into the sedimentation chamber, rotating the substrate about an axis of rotation at a first rotational speed to separate the plasma from blood cells, and rotating the substrate about the axis of rotation at a second rotational speed, which is lower than the first rotational speed, to move the plasma from the sedimentation chamber into the collection chamber.
Core Innovation
The invention is a centrifugal microfluidic device, particularly a CD-based (compact disc-based) device, designed for integrated sample preparation and separation of plasma from large-volume undiluted whole blood samples. The device consists of a multilayer substrate, incorporating a sedimentation chamber with a plurality of finger-like structures along the radially outward edge, a collection chamber in fluidic communication with the sedimentation chamber via a siphon channel, and additional features including ventilation channels and sample inlets/outlets.
The device operates by introducing a whole blood sample into the sedimentation chamber, spinning the device at a first rotational speed to sediment cells and separate the plasma, then reducing the speed to allow plasma to move into the collection chamber through capillary-primed siphon action. This mechanism automates the plasma collection process and yields highly pure plasma, while mitigating common issues in processing large sample volumes, such as delamination, leakage, and inadequate separation.
The problem being addressed is that existing continuous flow and microfluidic devices for blood separation are not well suited for high hematocrit samples and generally require the dilution of blood, leading to longer run times and additional processing steps. The centrifugal device of the invention provides a means to process large volumes of undiluted blood efficiently and yields plasma of high purity without the need for additional manual pipetting or extended centrifugation protocols.
Claims Coverage
The patent contains two independent claims, each covering a different aspect of the device for plasma separation from whole blood, focusing on the device's structure and operation.
Multilayer substrate with sedimentation and collection chambers
A centrifugal device features a multilayer substrate (such as a compact disc), having an axis of rotation and comprising: - A sedimentation chamber disposed in one layer of the substrate, with an interior volume of at least 2 mL, and possessing a plurality of finger-like structures along the radially outward edge, protruding radially inward relative to the axis of rotation into the chamber. - A collection chamber disposed in the substrate and in fluidic communication with the sedimentation chamber. The device can include various additional channels, such as siphon, ventilation, and sample inlet/outlet channels, as further specified in dependent claims.
Integrated inlet, siphon, and ventilation structure for plasma separation
A centrifugal device comprising: - A multilayer substrate with an inlet channel including an inlet hole, and a sedimentation chamber with a volume of at least 2 mL and finger-like structures disposed along the radially outward edge, protruding inward. - A collection chamber, at least part of which is radially outward of the sedimentation chamber, in fluidic communication with the sedimentation chamber via a siphon channel. - A ventilation channel disposed in the substrate, connecting the sedimentation and collection chambers. This configuration enables handling larger blood sample volumes and helps maintain device integrity through fluid transfer.
The inventive features claimed include a multilayer centrifugal device with a specifically designed sedimentation chamber featuring finger-like structures for enhanced bonding and pressure handling, coupled with a collection chamber and fluidic channels to enable automated, high-purity plasma separation from whole blood.
Stated Advantages
Capable of processing large-volume (at least 2 mL) undiluted whole blood samples to yield high purity plasma in less than half the time of commercial plasma preparation tubes.
Automates plasma collection into a separate chamber, removing the additional step of manual pipetting and reducing risk of cell resuspension.
Provides higher or equal plasma purity compared to commercial tube formats for the same duration of sedimentation time.
Reduces or eliminates delamination and fluid leakage during large-volume processing through the use of finger-like structures and thicker polycarbonate layers.
Allows for fully sealed sample handling which minimizes exposure to users and environmental contamination.
Documented Applications
Separation of plasma from whole blood samples for sample preparation in analytical and diagnostic contexts.
General separation of components in other biological samples, such as saliva, urine, and milk.
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