System and method for immune activity determination
Inventors
Tse, Henry Tat Kwong • Shah, Ajay M. • Guillou, Lionel • Sheybani, Roya • Dahlberg, Christopher • JENSEN, Anne E.
Assignees
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Publication Number
US-11123734-B2
Publication Date
2021-09-21
Expiration Date
Abstract
A system and method for determining a trajectory parameter of particles, comprising receiving a plurality of particles at a microfluidic channel, applying a force to each particle of the microfluidic channel, acquiring a dataset of each particle, measuring a trajectory of the particle, and determining a trajectory parameter of the particles.
Core Innovation
The disclosed invention relates to a microfluidic cytometry system and method for determining a trajectory parameter associated with blood cells of a subject. The method receives a plurality of blood cells at a microfluidic channel, aligns and focuses the plurality of blood cells at an inertial focusing region, applies a stress at a deformation region downstream of the focusing region, and acquires an optical dataset of each cell as the cell passes through the deformation region.
The trajectory of each cell is measured as a series of discrete positions and includes an oscillation of a centroid of the cell. The invention determines one or more trajectory parameters associated with the subject, where the trajectory parameters comprise at least one of a difference, sum, amplitude, maximum, and average value of one or more positions of the trajectory. The approach converts centroid oscillations during stress application into quantitative trajectory parameters.
A related diagnostic method determines immune activation state by combining trajectory and structural readouts derived from optical imaging. The method receives a plurality of blood cells of a patient at a microfluidic channel, applies a stress at a deformation region configured to deform the cell, acquires an optical dataset comprising a plurality of images before, during, and after the stress, determines a structural parameter using the plurality of images, determines a trajectory parameter based on oscillation of the centroid during and after the stress, and determines an immune-state index using a model correlating the trajectory parameters and the structural parameters.
Claims Coverage
The partial content contains two independent claims directed to trajectory-parameter determination and to diagnosing immune activation state. Across these claims, the inventive coverage centers on inertial focusing in a microfluidic channel, applying stress in a downstream deformation region, acquiring optical datasets during cell passage, measuring centroid-oscillation-based trajectories as discrete positions, and deriving quantitative trajectory and structural parameters that are correlated to an immune-state index by a model.
Inertial focusing of blood cells in a microfluidic channel
A method receives a plurality of blood cells at a microfluidic channel and aligns and focuses the plurality of blood cells at an inertial focusing region of the microfluidic channel.
Downstream deformation-region stress with optical imaging
For each cell, a stress is applied at a deformation region downstream of the focusing region, and an optical dataset is acquired as the cell passes through the deformation region; in the diagnostic method, the dataset comprises a plurality of images before, during, and after the stress is applied.
Centroid-oscillation trajectory measured as discrete positions and converted to trajectory parameters
The method measures a trajectory comprising a series of discrete positions, where the trajectory comprises an oscillation of a centroid of the cell, and determines trajectory parameters associated with the subject that comprise at least one of a difference, sum, amplitude, maximum, and average value of one or more positions of the trajectory.
Structural parameter determination from plurality of images
The diagnostic method determines a structural parameter associated with the cell using the plurality of images acquired before, during, and after the stress is applied to the cell.
Immune-state index from model correlating trajectory and structural parameters
Based on a model correlating the trajectory parameters and the structural parameters to an immune state, the diagnostic method determines an index associated with the patient and diagnoses the immune activation state based on the index.
Overall, the independent-claim coverage spans inertial focusing in a microfluidic channel, stress application in a downstream deformation region with optical dataset acquisition, measurement of centroid-oscillation trajectories as discrete positions and computation of trajectory parameters, and, for diagnosis, combining trajectory parameters with image-derived structural parameters in a model to determine an immune-state index for diagnosing immune activation state.
Stated Advantages
Improved accuracy/specificity/speed for determining immune activation, including sepsis-related.
Rapid diagnosis using high-frame-rate imaging.
Reproducible flow conditions.
Temperature control.
Documented Applications
Determining immune activation, including sepsis-related condition, from blood cells.
Diagnosing the immune activation state of a patient based on an index derived from trajectory and structural parameters.
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