IP Library Granted Patent US 11,123,734
Granted Patent B2
US 11,123,734 · App. 16/943,716 · Granted Sep 21, 2021

System and method for immune activity determination

Inventors: Henry Tat Kwong Tse (San Francisco, CA); Ajay M. Shah (San Francisco, CA); Lionel Guillou (San Francisco, CA); Roya Sheybani (San Francisco, CA); Christopher Dahlberg (San Francisco, CA); Anne E. Jensen (San Francisco, CA)
Assignee: CytoVale Inc.
B01L3/502761B01L3/502715B01L3/502746B01L3/502753G06N3/02G06T7/0012B01L2200/0631B01L2200/0652B01L2200/0668B01L2200/0684B01L2200/0694B01L2200/12B01L2300/0877B01L2300/0887B01L2300/185B01L2400/0409B01L2400/0415B01L2400/0436G06T2207/30024G06T2207/30104
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Quick Facts
Patent No.
US 11,123,734
App. No.
16/943,716
Granted
Sep 21, 2021
Kind
B2
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.

Claims (38)

1. A method for determining a trajectory parameter associated with blood cells of a subject, comprising:

receiving a plurality of blood cells of the subject at a microfluidic channel;

aligning and focusing the plurality of blood cells at an inertial focusing region of the microfluidic channel;

for each cell of the plurality of blood cells:

applying a stress to the cell at a deformation region of the microfluidic channel, wherein the deformation region is downstream of the focusing region;

with an image acquisition system, acquiring an optical dataset of the cell as the cell passes through the deformation region; and

measuring a trajectory of the cell passing through the deformation region, wherein the trajectory comprises a series of discrete positions of the cell as the cell passes through the deformation region, wherein the trajectory comprises an oscillation of a centroid of the cell; and

determining one or more trajectory parameters associated with the subject, wherein the trajectory parameters comprise at least one of a difference, sum, amplitude, maximum, and average value of one or more positions of the trajectory.

2. The method of claim 1 , wherein the oscillation is in a position orthogonal to the flow direction and the trajectory parameter comprises an average amplitude of the oscillation.

3. The method of claim 2 , wherein the trajectory parameter is determined based on a ternary, quaternary, and quintenary cycle of the oscillation.

4. The method of claim 2 , wherein the trajectory parameter is determined without using the first oscillation cycle.

5. The method of claim 1 , wherein the trajectory parameter is associated with an immune activation state of the subject.

6. The method of claim 1 , wherein the optical dataset comprises at least ten images of the cell within the deformation region.

7. The method of claim 1 , wherein a fluid flow through the microfluidic device is at a Reynolds number of at least 100.

8. The method of claim 1 , wherein the deformation region comprises an extensional flow region.

9. A method for diagnosing immune activation state of a patient, comprising:

receiving a plurality of blood cells of the patient at a microfluidic channel of a flow guide;

for each cell of the plurality of blood cells:

applying a stress to the cell at a deformation region of the flow guide, wherein the stress is configured to deform the cell;

with an image acquisition system, acquiring an optical dataset of the cell comprising a plurality of images of the cell before, during, and after the stress is applied to the cell;

determining a structural parameter associated with the cell, wherein the structural parameter is determined using the plurality of images; and

determining a trajectory parameter associated with a trajectory of the cell during and after the stress is applied to the cell, wherein the trajectory parameter comprises an oscillation of a centroid of the cell, wherein the trajectory parameter is determined based on the plurality of images;

based on a model correlating the trajectory parameters and the structural parameters to an immune state, determining an index associated with the patient; and

diagnosing the immune activation state of the user based on the index.

10. The method of claim 9 , wherein for each cell wherein the trajectory parameter comprises an amplitude of the oscillation.

11. The method of claim 10 , wherein for each cell, the trajectory parameter is determined based on an amplitude of a ternary, quaternary, and quintenary cycle of the oscillation.

12. The method of claim 9 , further comprising determining a leukocyte count of the plurality of blood cells, wherein the index is further determined based on the leukocyte count.

13. The method of claim 9 , wherein receiving the plurality of blood cells comprises receiving at least 100 cells per second at the flow guide.

14. The method of claim 9 , wherein determining the trajectory parameter comprises:

detecting an object within each image of the plurality of images;

segmenting each image of the plurality of images into a foreground and a background; and

extracting a feature from the foreground, wherein the feature is associated with at least one of a cell shape and the trajectory.

15. The method of claim 14 , wherein segmenting each image comprises segmenting each image using a convolutional neural network.

16. The method of claim 9 , further comprising lysing red blood cells of the plurality of blood cells using a formic acid lysis system.

17. The method of claim 9 , wherein the diagnosis is determined within 10 minutes of receiving the plurality of blood cells at the flow guide.

18. The method of claim 9 , wherein the immune activation state comprises a sepsis-related condition.

19. The method of claim 9 , wherein the model is a linear logistic regression.

20. The method of claim 19 , further comprising determining a set of parameters of the linear logistic regression using a training dataset corresponding to a patient set comprising a high sepsis incidence.

Assignments (5)
SECURITY INTEREST Recorded Sep 17, 2024
From: CYTOVALE INC.
To: VENTURE LENDING & LEASING IX, INC.
Reel/Frame 068609/0123 →
RELEASE OF SECURITY INTEREST Recorded Feb 15, 2024
From: VENTURE LENDING & LEASING IX, INC.
To: CYTOVALE INC.
Reel/Frame 066475/0941 →
CORRECTIVE ASSIGNMENT TO CORRECT THE PROPERTY TYPE LABEL FROM APPLICATION NO. 10252260 TO PATENT NO. 10252260, AND REMOVE APPLICATION NO. 10252260 FROM PREVIOUSLY RECORDED ON REEL 056580 FRAME 0472. ASSIGNOR(S) HEREBY CONFIRMS THE THE IP SECURITY AGREEMENT. Recorded Jan 23, 2024
From: CYTOVALE INC.
To: VENTURE LENDING & LEASING IX, INC.
Reel/Frame 066399/0836 →
SECURITY INTEREST Recorded Jun 17, 2021
From: CYTOVALE INC.
To: VENTURE LENDING & LEASING IX, INC.
Reel/Frame 056580/0472 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 7, 2021
From: KWONG TSE, HENRY TAT; SHAH, AJAY M.; GUILLOU, LIONEL; SHEYBANI, ROYA; DAHLBERG, CHRISTOPHER; JENSEN, ANNE E.
To: CYTOVALE INC.
Reel/Frame 054843/0886 →
Continuity (2)
Provisional Application 62881283 · Jul 31, 2019
Related Publication 20210031198A1 · Feb 4, 2021
Cited By (1)
US 12,478,966