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-12025542-B2
Publication Date
2024-07-02
Expiration Date
Abstract
A method and/or system can include processing a blood sample of a patient by degrading red blood cells of the blood sample using a lysing solution, quenching the degradation of the red blood cells after a threshold lysing time, centrifuging and aspirating the quenched solution to remove degraded red blood cell debris and concentrate white blood cells of the blood sample, and suspending the concentrated white blood cells in a buffer solution; within a threshold transfer time, deforming white blood cells, of the suspended white blood cells, within a microfluidic chip; and determining a probability that the patient is in an immune activation state based on images of the white blood cells acquired while deforming the white blood cells.
Core Innovation
A method is provided for assessing a patient immune activation state using a blood sample. The method processes the blood sample by degrading red blood cells with a lysing solution and quenching the degradation after a threshold lysing time, then centrifuging and aspirating the quenched solution to remove degraded red blood cell debris and concentrate white blood cells, and suspending the concentrated white blood cells in a buffer solution.
Within a threshold transfer time of processing the blood sample, the method deforms white blood cells in a microfluidic chip by applying at least one of a stress, a strain, a pressure, or a force. The deformation is performed so that a plurality of images of the white blood cells are acquired while deforming the white blood cells.
A probability that the patient is in an immune activation state is determined based on the plurality of images acquired during deformation. The described approach is used to assess an immune activation state such as sepsis, including in emergency department triage.
Claims Coverage
The document provides one independent method claim directed to a workflow that couples rapid blood preprocessing with microfluidic deformation cytometry and image-based probability scoring for an immune activation state. The independent claim contains 5 main inventive features.
Threshold-timed red blood cell degradation and quenching
Degrading red blood cells of the blood sample using a lysing solution, and quenching the degradation of the red blood cells after a threshold lysing time.
White blood cell isolation by debris removal and suspension
Centrifuging and aspirating the quenched solution to remove degraded red blood cell debris and concentrate white blood cells, and suspending the concentrated white blood cells in a buffer solution.
Microfluidic white blood cell deformation within a threshold transfer time
Within a threshold transfer time of processing the blood sample, deforming white blood cells by applying at least one of a stress, a strain, a pressure, or a force to the white blood cells within a microfluidic chip.
Image acquisition during deformation
Acquiring a plurality of images of the white blood cells while deforming the white blood cells.
Probability scoring from images using an average and standard deviation of white blood cells
Determining a probability that the patient is in an immune activation state based on an average of 55,000 white blood cells with a standard deviation of 35,000 white blood cells, wherein determining the probability is based on the plurality of images acquired while deforming the white blood cells.
Overall, the claim coverage is focused on rapidly processing a blood sample to isolate white blood cells, deforming the white blood cells in a microfluidic chip within a threshold transfer time, and determining a patient-level probability of an immune activation state using a plurality of images acquired during deformation and based on a specified average and standard deviation of white blood cells.
Stated Advantages
Reproducibility and reliability.
Reduced user error via automation.
Documented Applications
Emergency department triage to assess a patient immune activation state.
Immune activation state assessment for sepsis.
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