System and method for determining an immune activation state
Inventors
Tse, Henry Tat Kwong • Shah, Ajay M. • Guillou, Lionel • Malkin, Alexander • JENSEN, Anne E. • Martinez, Nicholas • Colegrove, Carissa • Voyen, Laura
Assignees
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Publication Number
US-11548003-B1
Publication Date
2023-01-10
Expiration Date
Abstract
A system or method for detecting an immune system activation state in a patient can include a sample preparation system configured to isolate white blood cells from a sample of the patient, a cytometry module configured to determine biophysical properties of the white blood cells of the sample, and an analysis module configured to analyze the biophysical properties.
Core Innovation
The invention relates to a system for detecting an immune system activation state in a patient using biophysical properties of white blood cells derived from a patient blood sample. The system includes a sample preparation system configured to lyse red blood cells while quenching the lysing reaction before white blood cells are damaged and to separate the white blood cells from the lysed red blood cells. The sample preparation system maintains a temperature of the blood sample between 24–26° C.
The cytometer is configured to determine biophysical properties of the white blood cells using a microfluidic channel architecture. The microfluidic channel includes an inlet configured to receive the separated white blood cells, a focusing region fluidly connected to the inlet through a filter to align the white blood cells, a deformation region fluidly connected to the focusing region to deform the white blood cells, and an outlet fluidly connected to the deformation region through a second filter.
A processor detects the immune system activation state in the patient based on the biophysical properties determined by the cytometer. The biophysical properties can comprise a trajectory parameter, including an oscillation of a centroid of a cell of the white blood cells, and detection can be performed using the processor with biophysical-property-based analysis to output an immune activation state.
Claims Coverage
The document provides two independent claims. Across the independent claims, the core coverage centers on sample preparation that lyses red blood cells while protecting white blood cells and controlling sample temperature, a microfluidic cytometer that determines biophysical properties via a focusing and deformation region, and a processor that detects the immune system activation state from the biophysical properties, with a trajectory-centroid oscillation limitation in the second independent claim.
Lysis, quench, separation, and temperature-controlled sample preparation
A sample preparation system configured to lyse red blood cells from a blood sample, quench the lysing reaction before white blood cells from the blood sample are damaged, separate the white blood cells from the lysed red blood cells, and maintain a temperature of the blood sample between 24–26° C.
Microfluidic cytometer with inlet, focusing region, deformation region, and outlet through filters
A cytometer configured to determine biophysical properties of the white blood cells of the sample, the cytometer comprising a microfluidic channel with an inlet to receive the separated white blood cells, a focusing region fluidly connected to the inlet through a filter to align the white blood cells, a deformation region fluidly connected to the focusing region to deform the white blood cells, and an outlet fluidly connected to the deformation region through a second filter.
Processor detecting immune activation state based on biophysical properties
A processor configured to detect the immune system activation state in the patient based on the biophysical properties.
Trajectory parameter as centroid oscillation for immune activation detection
The biophysical properties comprise a trajectory parameter, wherein the trajectory parameter comprises an oscillation of a centroid of a cell of the white blood cells.
Independent claim coverage broadly requires temperature-controlled lysis, quench, and separation of patient blood, microfluidic cytometry via inlet-focusing-deformation-outlet regions with filters, and processor-based detection of immune system activation state from biophysical properties. The second independent claim further limits the biophysical properties to a trajectory parameter defined as an oscillation of a cell centroid.
Stated Advantages
Documented Applications
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