US-20260126431-A1 - RAPID MOBILE SCREENING AND TRIAGE FOR INFECTIONS AND INFECTION SEVERITY

US20260126431A1US 20260126431 A1US20260126431 A1US 20260126431A1US-20260126431-A1

Abstract

A method of analyzing a blood sample from a subject includes loading the blood sample into a single chamber; acquiring, via an imaging system, a stack of serial focal plane images of the blood sample from a plurality of fields of view of the chamber; creating a virtual three dimensional image of the blood sample from selected ones of the stacks of serial focal plane images; and analyzing the virtual three dimensional image to identify blood formed elements within the blood sample. Identifying blood formed elements within the blood sample may include identifying a type and amount of white blood cells, and/or identifying an amount of red blood cells and/or hematocrit, and/or identifying an amount of platelets. Identifying blood formed elements within the blood sample may include determining numbers and percentage by volume in the blood sample of one or more types of white blood cells.

Inventors

Joy Parr Drach
Brendan Smith
Tobias M. Heineck
Stefano Bresolin
Rodolfo R. Rodriguez
Danielle Stewart Noel
Brian Pike
Oleg Kakhovsky
Jasper N. Pollard

Assignees

Advanced Animal Diagnostics, Inc.

Dates

Publication Date: 20260507
Application Date: 20251105

Claims (20)

1 . A method of analyzing a blood sample from a subject, the method comprising: loading the blood sample into a single chamber; acquiring, via an imaging system comprising a single camera, a stack of serial focal plane images of the blood sample from a plurality of fields of view of the chamber; creating a virtual three dimensional image of the blood sample from selected ones of the stacks of serial focal plane images; and analyzing the virtual three dimensional image to identify blood formed elements within the blood sample; wherein the chamber comprises at least one metachromatic stain in a dry format, and wherein the imaging system comprises a red-green-blue (RGB) detector sensitive to light across the visible spectrum.
2 - 14 . (canceled)
15 . The method of claim 1 , wherein the at least one metachromatic stain comprises a first stain configured to enhance cell membrane fluorescence and cytoplasm fluorescence, and a second stain configured to enhance nuclear fluorescence.
16 . The method of claim 1 , further comprising using independent RGB channels of the RGB detector to create the virtual three dimensional image of the blood sample from the selected ones of the stacks of serial focal plane images.
17 . The method of claim 1 , wherein analyzing the virtual three dimensional image to identify blood formed elements within the blood sample comprises processing the virtual three dimensional image using machine vision segmentation.
18 . The method of claim 1 , wherein the plurality of fields of view comprise at least twenty-five fields of view, preferably at least fifty fields of view, and even more preferably at least one hundred fields of view.
19 - 22 . (canceled)
23 . A method of managing a subject having an infection, comprising: a) carrying out the method of claim 1 at least two times; b) classifying the subject as: 1) no change in the infection; 2) improving of the infection; or 3) worsening of the infection based on the results of step a); and c) managing the subject based on the results of step b).
24 . A method of managing a subject having a SARS-CoV2 infection, comprising: a) carrying out the method of claim 1 at least two times; b) classifying the subject as: 1) no change in the SARS-CoV2 infection; 2) improving of the SARS-CoV2 infection; or 3) worsening of the SARS-CoV2 infection based on the results of step a); and c) managing the subject based on the results of step b).
25 . A method of managing a subject having sepsis, comprising: a) carrying out the method of claim 1 at least two times; b) classifying the subject as: 1) no change in the sepsis; 2) improving of the sepsis; or 3) worsening of the sepsis based on the results of step a); and c) managing the subject based on the results of step b).
26 . A method of monitoring a subject for a potential infection, comprising: a) carrying out the method of claim 1 b) classifying the subject as: 1) unlikely to have an infection; 2) likely to have an infection; or 3) likely to have an infection with severe symptoms based on the results of step a); and c) managing the subject based on the results of step b); wherein the subject has no symptoms of an infection; and/or wherein the method is carried out on the subject more than once to monitor for the appearance of an infection.
27 - 38 . (canceled)
39 . A portable apparatus, comprising: a processor; a hematology analyzer in communication with the processor; and a tangible, non-transitory memory configured to communicate with the processor, the tangible, non-transitory memory having instructions stored thereon that, in response to execution by the processor, cause the processor to perform operations comprising: receiving from the hematology analyzer, a stack of serial focal plane images of a blood sample in a chamber from a plurality of fields of view of the chamber; creating a virtual three dimensional image of the blood sample from selected ones of the stacks of serial focal plane images; and analyzing the virtual three dimensional image to identify blood formed elements within the blood sample; wherein analyzing the virtual three dimensional image to identify blood formed elements within the blood sample comprises identifying a type and amount of white blood cells; and/or analyzing the virtual three dimensional image to identify blood formed elements within the blood sample comprises identifying an amount of red blood cells and/or hematocrit; and/or analyzing the virtual three dimensional image to identify blood formed elements within the blood sample comprises identifying an amount of platelets; and/or analyzing the virtual three dimensional image to identify blood formed elements within the blood sample comprises determining numbers and percentage by volume in the blood sample of one or more types of white blood cells.
40 - 43 . (canceled)
44 . The apparatus of claim 39 , wherein the one or more types of white blood cells are selected from the following: lymphocytes, neutrophils, eosinophils, basophils, monocytes, bands, and immature granulocytes, optionally wherein the immature granulocytes include band neutrophils, metamyelocytes, myelocytes, and blasts.
45 . (canceled)
46 . The apparatus of claim 39 , wherein analyzing the virtual three dimensional image to identify blood formed elements within the blood sample comprises determining ratio in the blood sample of two or more types of white blood cells, optionally comprising determining the ratio of neutrophils to lymphocytes.
47 . (canceled)
48 . The apparatus of claim 46 , wherein the tangible, non-transitory memory further has instructions stored thereon that, in response to execution by the processor, cause the processor to perform operations comprising using the determined numbers, percentage by volume, and ratios in the blood sample of the one or more types of white blood cells to determine a likelihood that the subject has an infection and/or a severity of the infection.
49 . The apparatus of claim 39 , wherein the tangible, non-transitory memory further has instructions stored thereon that, in response to execution by the processor, cause the processor to perform operations comprising using optical information from at least one image in a stack of images of a first field of view to select optical parameters utilized during the acquiring of a stack of serial focal plane images in a second, subsequent field of view, optionally wherein the optical parameters comprise one or more of the following: exposure time, camera gains, and illumination intensity.

Description

STATEMENT OF PRIORITY This application is a continuation of and claims priority to U.S. patent application Ser. No. 17/905,990, filed Sep. 9, 2020, which is a 35 U.S.C. §371 national phase application of PCT Application PCT/US2021/022167 filed Mar. 12, 2021, which claims the benefit of U.S. Provisional Application Ser. No. 62/989,283, filed Mar. 13, 2020, the entire contents of each of which are incorporated by reference herein. BACKGROUND The Covid 19 pandemic has highlighted limitations in the healthcare system on its ability to deliver host-based, accurate diagnostic information about an individual's health and immune system status, especially infections, in a timely manner. Adverse outcomes can arise from almost any infection, and lack of ability to predict or identify these complications early when infection is present may create a challenge to effective patient management, as well as a failure to appropriately allocate resources. In the current pandemic, the great majority of individuals infected with SARS-CoV-2 have a mild illness, a smaller percentage experience moderately severe disease, and only very few require critical care. It has been challenging for hospitals, overwhelmed with patients and limited in resources, to quickly and accurately identify patients who require hospital admission or ICU care and separate them from those at low risk of complications, who can be sent home or to a lower-level care facility. Triage decisions by necessity may have been made based on subjective, ad-hoc clinical judgment. Sepsis is one the most common severe complication of COVID-19 infection, or any other infection, representing the host's extreme response to that infection, and may eventually lead to organ dysfunction and death. Individual comorbidities, pathogen, genotype, phenotype as well as the relative strength of the individual immune system, may cause the response to infection to vary substantially among patients. This heterogeneity of response may make it difficult for triage personnel to determine infection severity, or disease progression, possibly delaying successful intervention. The inability to quickly determine infection severity and properly triage infected patients who are at higher risk for health deterioration, sepsis or poor outcomes, adversely affects the health care system's ability to provide the required and timely care to patients who need it. This is especially true in certain areas of the country, where rapid host-based diagnostic testing is scarce, and a disproportionate amount of these areas are in rural and low-income areas. When tests are available, they cannot always differentiate those who must be rushed to a hospital from those who can be sent home or can self-quarantine. The need for rapid information is especially important in transient populations, such as homeless shelters, where caregivers may not be able to find the patient later to provide results. Results must be available patient-side in a matter of seconds. In addition, the equipment needed to provide results must be robust enough to operate in a variety of point-of-care settings including outdoor or drive-through testing facilities. It would be highly desirable to be able to recognize infection severity at early points in its progression in order to allow for tailored intervention to reduce adverse outcomes. SUMMARY In one aspect, the present disclosure provides a method of analyzing a blood sample from a subject that includes loading the blood sample into a single chamber; acquiring, via an imaging system, a stack of serial focal plane images of the blood sample from a plurality of fields of view of the chamber; creating a virtual three dimensional image of the blood sample from selected ones of the stacks of serial focal plane images; and analyzing the virtual three dimensional image to identify blood formed elements within the blood sample. In some embodiments, the plurality of fields of view comprise at least twenty-five fields of view, preferably at least fifty fields of view, and even more preferably at least one hundred fields of view. In some embodiments, the method is performed by a portable automated microscope apparatus at a location of the subject. In some embodiments, analyzing the virtual three dimensional image to identify blood formed elements within the blood sample comprises identifying a type and amount of white blood cells, and/or identifying an amount of red blood cells and/or hematocrit, and/or identifying an amount of platelets. In some embodiments, analyzing the virtual three dimensional image to identify blood formed elements within the blood sample comprises determining numbers and percentage by volume in the blood sample of one or more types of white blood cells. The one or more types of white blood cells may be selected from the following: lymphocytes, neutrophils, eosinophils, basophils, monocytes, bands, and immature granulocytes. The immature granulocytes may include band neutrophils,