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-11592371-B1
Publication Date
2023-02-28
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
The invention provides a method for diagnosing sepsis in a patient by preparing a preheated microfluidic chip and processing a blood sample to obtain white blood cells. The blood sample is mixed with a formic acid solution to degrade red blood cells, and after a lysing time the sample is quenching with a quenching solution. After a quenching time, the blood sample is washed to remove lysed red blood cells from the white blood cells, and the white blood cells are resuspended in a buffer solution.
Within a threshold time of resuspending the white blood cells, the method transfers the white blood cells in the buffer solution to the preheated microfluidic chip. The white blood cells are deformed within a deformation region of the microfluidic chip, and images of the white blood cells are acquired during deformation using the imaging system. The preheating to a target temperature and the time constraint for transfer are used as part of the controlled measurement workflow.
Sepsis is diagnosed based on features extracted from the acquired images of the white blood cells. The features include trajectory parameters, cell count, and leukocyte subpopulations, and the diagnosis uses features derived from image analysis of the deformed white blood cells. The method implements an automated sample preparation sequence and subsequent microfluidic deformation and imaging, combined with computing based on extracted biophysical and trajectory information to generate a diagnostic probability or score.
Claims Coverage
The independent claim covers a sepsis diagnosis method that integrates timed and temperature-controlled microfluidic chip preparation, acid lysis with quenching and washing to obtain white blood cells, within-threshold-time transfer into the microfluidic deformation region, deformation imaging, and image-derived feature-based diagnosis using trajectory parameters, cell count, and leukocyte subpopulations. Dependent claims further refine timing and processing constraints, with additional temperature dependency and an aspirating/centrifuging washing refinement.
Preheated microfluidic chip for time-bounded sepsis diagnosis
The method includes preheating a microfluidic chip to a target temperature and transferring the white blood cells in the buffer solution to the preheated microfluidic chip within a threshold time of resuspending the white blood cells.
Formic-acid lysis, quenching, and washing workflow to isolate white blood cells
The method mixes a blood sample with a formic acid solution to degrade red blood cells, quenches with a quenching solution after a lysing time, and washes after a quenching time to remove lysed red blood cells from white blood cells.
Microfluidic deformation and image acquisition of white blood cell trajectories
The method deforms the white blood cells within a deformation region of the microfluidic chip and acquires images of the white blood cells during deformation.
Image-derived feature extraction for diagnosing sepsis from trajectory and subpopulation features
The method diagnoses sepsis in the patient based on features extracted from the images of the white blood cells, wherein the features comprise trajectory parameters, cell count, and leukocyte subpopulations.
Overall, the independent claim ties together preheated microfluidic chip operation with formic-acid lysis/quenching and washing to isolate white blood cells, time-bounded transfer into a deformation region, imaging during deformation, and sepsis diagnosis using image-extracted trajectory parameters, cell count, and leukocyte subpopulations.
Stated Advantages
Improved reproducibility and reliability through standardized or autonomous processing.
Reduced user error through automated, timed, and temperature-controlled processing steps.
Documented Applications
Diagnosing sepsis in a patient using blood-sample processing and microfluidic deformation imaging with image-derived diagnostic features.
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