System and method for deforming particles

Inventors

Tse, Henry • Crawford, Kate • Shah, Ajay

Assignees

Cytovale Inc

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Publication Number

US-10252260-B2

Patent

Publication Date

2019-04-09

Expiration Date


Abstract

Embodiments of a system and method for deforming a can include a substrate including an inlet module and an outlet module; a fluidic pathway coupled to the inlet module and the outlet module, and including a sample branch operable to transmit the sample fluid; one or more sheath fluid branches flanking the sample branch and operable to transmit sheath having a sheath fluid viscosity higher than a sample fluid viscosity of the sample fluid; a delivery region initiating at a junction between the sample branch and the one or more sheath fluid branches, and operable to transmit a co-flow comprising the sample fluid and the sheath fluid; and a deformation region located downstream of the delivery region and operable to deform the one or more particles of the sample fluid based upon a reduced velocity of the sheath fluid with respect to the sample fluid in the co-flow.

Core Innovation

The invention provides a method for characterizing deformation of a first particle in a sample fluid using a microfluidic system with a delivery region and a downstream deformation region. A sheath fluid pinches the sample fluid at the delivery region to generate a first co-flow comprising the sheath fluid and the sample fluid, and the first co-flow is transmitted from the delivery region to the deformation region while the sheath fluid viscosity is greater than the sample fluid viscosity.

At the deformation region, the first particle is deformed based upon a change in velocity of the sheath fluid with respect to the sample fluid in the first co-flow. The deformation includes applying an increased stress on particle peripheral regions positioned in the sheath fluid of the first co-flow at the deformation region, and the described microfluidic pathway includes sequential narrowing, straight, and expanding elements that form a deformation sequence with repeated stress and relaxation cycles.

The invention further captures an optical dataset of the first particle traveling through the deformation region and determines a morphology dataset describing the deformation of the first particle at the deformation region based on the optical dataset. The morphology dataset is computed from deformation metrics, including a bullet metric generated using a particle-wall trace, a polar transform, and discrete Fourier transform harmonics.

Claims Coverage

The independent claim covers three inventive features: sheath-fluid pinching to form a co-flow with a viscosity mismatch, deformation at a downstream deformation region based on velocity change and increased peripheral-region stress, and optical capture followed by determination of a morphology dataset. Dependent claims further refine repeated stress and relaxation cycles and Fourier-based morphology extraction.

Sheath-fluid pinching to form a co-flow with higher viscosity mismatch

Receiving the sample fluid at a delivery region of a fluidic pathway and receiving a sheath fluid at the delivery region, wherein the sheath fluid pinches the sample fluid to generate a first co-flow comprising the sheath fluid and the sample fluid, transmitting the first co-flow to a deformation region downstream, and wherein the sheath fluid possesses a sheath fluid viscosity greater than a sample fluid viscosity of the sample fluid while the first particle center is positioned in the sample fluid of the first co-flow at the deformation region.

Velocity-change-driven deformation with increased peripheral-region stress

Deforming the first particle at the deformation region based upon a change in velocity of the sheath fluid with respect to the sample fluid in the first co-flow, wherein deforming the first particle comprises applying an increased stress on particle peripheral regions positioned in the sheath fluid of the first co-flow at the deformation region.

Optical dataset capture and morphology dataset determination

Capturing an optical dataset of the first particle traveling through the deformation region and determining a morphology dataset describing the deformation of the first particle at the deformation region based on the optical dataset.

Repeated stress and relaxation cycles

Deforming the first particle at the deformation region comprises applying repeated stress and relaxation cycles, with deformation metrics versus particle x-position forming peaks and troughs at x-positions corresponding to the repeated cycles of stress and relaxation.

Fourier-harmonic deformation metric from particle wall trace

Determining a morphology dataset from an optical dataset by extracting a trace of a first particle wall, converting the trace to polar coordinates, applying a discrete Fourier transform, and computing a deformation metric from a harmonic of the discrete Fourier transform.

Across the independent claim and its refinements, deformation characterization is achieved by higher-viscosity sheath-fluid pinching to create a co-flow with the particle center in the sample fluid, deforming the particle at a downstream deformation region based on velocity change with increased stress on peripheral regions in the sheath fluid, and then capturing optical data to determine a morphology dataset.

Stated Advantages

Enables characterizing deformation of a first particle by linking co-flow-driven velocity change to increased stress on particle peripheral regions and then extracting deformation information from optical datasets.

Provides morphology datasets describing particle deformation based on optical datasets.

Supports dynamic characterization via deformation metrics with repeated stress and relaxation cycles and deformation-metric patterns versus particle x-position.

Provides deformation metrics computed from particle-wall trace transformed to polar coordinates and discrete Fourier transform harmonics.

Documented Applications

Characterizing deformation of leukocytes and correlating deformation-metric peak/trough behavior with a sepsis-related condition.

Measuring stiffness-dependent red blood cell deformation metrics.

Measuring oil droplet deformation metrics.

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