IP Library Granted Patent US 10,018,549
Granted Patent B2
US 10,018,549 · App. 15/132,906 · Granted Jul 10, 2018

Rapid measurement of formed blood component sedimentation rate from small sample volumes

Inventors: Mark Dayel (Palo Alto, CA); Samartha Anekal (Palo Alto, CA); Elizabeth A. Holmes (Palo Alto, CA)
Assignee: Theranos IP Company, LLC
G01N15/042G01N15/05G01N33/491G01N2015/0069G01N2015/0073G01N2015/045G01N2015/055
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Quick Facts
Patent No.
US 10,018,549
App. No.
15/132,906
Granted
Jul 10, 2018
Kind
B2
Abstract

Devices and methods are described for measuring formed blood component sedimentation rate. Some of the methods may use (1) centrifugal techniques for separating red blood cells from plasma and (2) video and/or still imaging capability. Both may be used alone or in combination to accelerate formed blood component sedimentation and to measure its rate. In one example, the method may advantageously enable rapid measurement of sedimentation rate using small blood sample volumes. Automated image analysis can be used to determine both sedimentation rate and hematocrit. Automated techniques may be used to compensate for effects of hematocrit on uncorrected sedimentation rate data.

Claims (37)

1. A method comprising:

using an accelerated blood component separation technique using a first compaction force on a blood sample for a first period of time, wherein the accelerated blood component separation technique occurs at a first module of a benchtop, point-of-service system and wherein the blood sample is contained in a non-capillary vessel;

moving the vessel from the first module to an imaging module all within a housing of the point-of-service system;

imaging the vessel to determine a position of formed component and plasma boundary in the vessel;

moving the vessel from the imaging module back to the first module;

using the accelerated blood component separation technique on the blood sample for a second period of time at a second compaction force greater than the first compaction force associated with the first period of time;

moving the vessel from the first module to an imaging module after the second period of time;

imaging the vessel to determine a second position of formed component and plasma boundary in the vessel after the second period of time;

determining a time-related compaction curve for at least one formed blood component in said blood sample after accelerated blood component separation based on the first position and the second position, said compaction curve having an initial approximately linear portion; and

determining sedimentation rate of the formed blood component in said accelerated blood component separation technique, based on at least the linear portion of the compaction curve and a hematocrit correction factor based on a hematocrit of the sample.

2. The method of claim 1 wherein the accelerated blood component separation technique comprises centrifuging the blood sample.

3. The method of claim 2 , wherein formed component and plasma boundary comprise an erythrocyte/plasma interface boundary.

4. The method of claim 2 , further comprising image transformation for conversion of a curved liquid interface to a flat interface.

5. The method of claim 2 , further comprising using a processor programmed to record interface position during a least a portion of centrifugation.

6. The method of claim 2 wherein the non-capillary vessel comprises a centrifuge vessel.

7. The method of claim 1 comprises correcting for hematocrit effect on sedimentation rate by using the hematocrit correction factor based on the formula:

U

corr

=

U

uncorr

(

1

-

φ

φ

max

)

γ

,

where U uncorr and U corr are the uncorrected (raw) and corrected sedimentation rates, φ is the volume fraction of cells (hematocrit), and φ max and γ are empirical parameters obtained by curve fitting.

8. The method of claim 7 wherein curve fitting for the hematocrit correction factor comprises calibrating sedimentation rates from centrifuge based technique with sedimentation rates from a reference technique.

9. The method of claim 8 , wherein the reference technique is the Westergren technique.

10. The method of claim 1 , wherein said blood sample is about 100 uL or less.

11. The method of claim 1 , wherein said blood sample is about 50 uL or less.

12. The method of claim 1 , wherein correcting for hematocrit comprises calculating a mathematical function for a plurality of formed blood component interface positions occurring in said curve, said function being operative to correct for sedimentation rate variations due to hematocrit.

13. The method of claim 1 wherein the blood sample being processed has a volume in the vessel of about 20-25 uL.

Assignments (5)
CHANGE OF NAME Recorded Apr 3, 2020
From: THERANOS IP COMPANY, LLC
To: LABRADOR DIAGNOSTICS LLC
Reel/Frame 052313/0011 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 16, 2018
From: THERANOS, INC.
To: THERANOS IP COMPANY, LLC
Reel/Frame 045101/0315 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 12, 2017
From: THERANOS INC.
To: THERANOS IP COMPANY, LLC
Reel/Frame 044838/0909 →
SECURITY INTEREST Recorded Dec 12, 2017
From: THERANOS IP COMPANY, LLC
To: FORTRESS CREDIT CORP.
Reel/Frame 044839/0568 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 19, 2016
From: DAYEL, MARK; ANEKAL, SAMARTHA; HOLMES, ELIZABETH A.
To: THERANOS, INC.
Reel/Frame 038465/0240 →
Continuity (3)
Continuation 13945147 · Jul 18, 2013
Provisional Application 61673037 · Jul 18, 2012
Related Publication 20160341650A1 · Nov 24, 2016