Blood sample analysis systems and methods

Patent metadata

Field	Value
Publication number	US-2020141920-A1
Application number	US-201816181849-A
Country	US
Kind code	A1
Filing date	Nov 6, 2018
Priority date	Nov 6, 2018
Publication date	May 7, 2020
Grant date	—

Abstract

A system includes an optical measurement unit that measures an optical property of a whole blood sample deposited on a surface of a substrate, an ion source that causes ions derived from the whole blood sample, including ions formed from an analyte of interest present in the whole blood sample, to be emitted from the substrate, a mass analyzer that receives the ions emitted from the substrate and measures an abundance of at least one ion species corresponding to the analyte of interest, and at least one computing device that determines, based on the measured optical property, a hematocrit of the whole blood sample, and determines, based on the determined hematocrit of the whole blood sample and the measured abundance of the at least one ion species, a concentration of the analyte of interest per unit volume of blood plasma.

First claim

What is claimed is:

1 . A system comprising:
an optical measurement unit configured to measure an optical property of a whole blood sample deposited on a surface of a substrate; an ion source configured to cause ions derived from the whole blood sample to be emitted from the substrate, wherein the ions emitted from the substrate include ions formed from an analyte of interest present in the whole blood sample; a mass analyzer configured to receive the ions emitted from the substrate and measure an abundance of at least one ion species corresponding to the analyte of interest; and at least one computing device configured to
determine, based on the measured optical property, a hematocrit of the whole blood sample, and
determine, based on the determined hematocrit of the whole blood sample and the measured abundance of the at least one ion species, a concentration of the analyte of interest per unit volume of blood plasma.

2 . The system of claim 1 , wherein the optical measurement unit comprises:
a light source configured to emit light to the whole blood sample, and a light sensor configured to detect at least one of (i) light reflected by the whole blood sample and (ii) light transmitted through the whole blood sample.

3 . The system of claim 2 , wherein the light source comprises a light emitting diode (LED), a laser, an incandescent lamp, a discharge lamp, or a combination thereof.

4 . The system of claim 1 , wherein the optical measurement unit comprises an optical spectrometer.

5 . The system of claim 1 , wherein the ion source includes a voltage source for applying a voltage to the substrate.

6 . The system of claim 5 , further comprising an automated liquid handler for applying a solvent to the whole blood sample.

7 . The system of claim 6 , wherein the substrate comprises a layer of porous material such that components of the whole blood sample are transported along the substrate by capillary action after the solvent is added to the whole blood sample.

8 . The system of claim 6 , wherein the automated liquid handler further applies one or more of a reagent and an internal standard to the whole blood sample.

9 . The system of claim 1 , wherein
the substrate is held by a cartridge, the optical measurement unit is further configured to support, during the measurement of the optical property of the whole blood sample, the cartridge in a first position such that light emitted by the optical unit is incident on the whole blood sample, and the ion source is further configured to support, during the emission of the ions from the substrate, the cartridge in a second position such that the ions are delivered to the mass analyzer.

10 . The system of claim 9 , further comprising a carriage configured to move the substrate from the first position to the second position.

11 . The system of claim 1 , wherein the analyte of interest present in the whole blood sample comprises hemoglobin A1c or creatinine.

12 . The system of claim 1 , wherein
the ions emitted from the substrate further include ions derived from one or more additional analytes of interest present in the whole blood sample, the mass analyzer is further configured to measure an abundance of one or more additional ion species corresponding to the one or more additional analytes of interest, and the at least one computing device is further configured to determine, based on the determined hematocrit of the whole blood sample and the measured abundance of the one or more additional ion species, a concentration of the one or more additional analytes of interest per unit volume of blood plasma.

13 . The system of claim 12 , wherein the analyte of interest and the one or more additional analytes of interest comprise components of a renal panel comprising creatinine, total hemoglobin, and an immunosuppressant.

14 . The system of claim 12 , wherein the analyte of interest and the one or more additional analytes of interest comprise components of a diabetes panel comprising hemoglobin A1c, creatinine, and total hemoglobin.

15 . The system of claim 12 , wherein the analyte of interest and the one or more additional analytes of interest are included in a panel of drugs of abuse.

16 . The system of claim 1 , wherein the mass analyzer comprises a quadrupole ion trap mass analyzer, a quadrupole mass filter, a time-of-flight mass analyzer, or an orbital electrostatic trap mass analyzer.

17 . The system of claim 1 , wherein the at least one computing device is further configured to provide, for presentation to a user, information indicating the concentration of the analyte of interest per unit volume of blood plasma.

18 . The system of claim 1 , further comprising:
an automated liquid handler configured to
withdraw a volume of whole blood from a whole blood specimen contained in a specimen container, and
deposit the whole blood sample on the surface of the substrate.

19 . A method, comprising:
measuring, by a blood sample analysis system, an optical property of a whole blood sample deposited on a surface of a substrate; determining, by the blood sample analysis system based on the measured optical property, a hematocrit of the whole blood sample; causing, by the blood sample analysis system, ions derived from the whole blood sample to be emitted from the substrate, the ions emitted from the substrate including ions of an analyte of interest present in the whole blood sample; receiving, by the blood sample analysis system at a mass analyzer, the ions emitted from the substrate; measuring, by the blood sample analysis system at the mass analyzer, an abundance of at least one ion species corresponding to the analyte of interest; and determining, by the blood sample analysis system based on the determined hematocrit of the whole blood sample and the measured abundance of the at least one ion species, a concentration of the analyte of interest per unit volume of blood plasma.

20 . An apparatus comprising:
a light source that causes light to be incident on a whole blood sample deposited on a surface of a substrate; a light sensor that detects, from the whole blood sample, a portion of the light incident on the whole blood sample; an ion source that generates ions from the whole blood sample by directly ionizing the whole blood sample, wherein the ions generated from the whole blood sample include ions formed from an analyte of interest present in the whole blood sample; a mass analyzer that detects, based on a ratio of mass to charge of the ions generated from the whole blood sample, an abundance of at least one ion species corresponding to the analyte of interest; and a physical computing device that determines, based on the detected portion of the light incident on the whole blood sample and the detected abundance of the at least one ion species, a concentration of the analyte of interest per unit volume of blood plasma.

Assignees

• Thermo Finnigan Llc

Inventors

• Glazier John
• Schwartz Jae C
• Tehlirian Berg A

Classifications

• H01J49/0036

  Step by step routines describing the handling of the data generated during a measurement · CPC title

• H01J49/0431

  for liquid samples (interfaces to liquid chromatographs G01N30/7233) · CPC title

• G01N33/49 Primary

  Blood {(chemical methods for determining blood cell populations G01N33/5094; chemical analysis of blood groups or blood types G01N33/80)} · CPC title

• G01N21/4738

  Diffuse reflection (precedence is given to G01N21/55 - G01N21/57 if specular component is taken into consideration), e.g. also for testing fluids, fibrous materials · CPC title

• H01J49/26

  Mass spectrometers or separator tubes · CPC title