IP Library › Granted Patent US 12,265,014
Granted Patent B2
US 12,265,014 · App. 18/367,705 · Granted Apr 1, 2025

Systems and methods for evaluating immune response to infection via monitoring cell granularity parameter of cells

Inventors: Liliana Tejidor (Coral Gables, FL); Robert T. Magari (Cooper City, FL); Diana Careaga (Miami, FL); Sanghyuk Shin (Carlsbad, CA)
Assignee: Beckman Coulter, Inc.
G01N15/1459G01N33/80G01N2015/012G01N2015/1006G01N33/48G01N2800/26G01N2800/52
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Quick Facts
Patent No.
US 12,265,014
App. No.
18/367,705
Granted
Apr 1, 2025
Kind
B2
Abstract

Systems and methods for characterizing immune response to infection using cellular analysis, such as a hematological cellular analyzer. In some instances, the immune response may be characterized as normal or abnormal based on one or more blood cell population parameters. In some instances, abnormal characterization may be used to identify patients with sepsis or at elevated risk of developing sepsis.

Claims (19)

1. A system for characterizing an inflammatory response to infection, the system comprising:

a. a transducer module configured to measure at least a cell granularity parameter of cells passing through a flowcell; and

b. a processor configured with instructions stored on a non-transitory computer readable medium and operable to, when executed and based on measurement data from the transducer module, detect whether a differentially expressed sepsis cell population parameter is present in a heterogenous population of circulating cells passing through the flowcell by performing steps comprising:

i. identifying one or more cells among the heterogenous population of circulating cells passing through the flowcell;

ii. obtaining a plurality of measurements, wherein the plurality of measurements comprises, for the one or more cells a measurement of the cell granularity parameter; and

iii. calculating a standard deviation of the measurements of the cell granularity parameter for the one or more cells.

2. The system of claim 1 , wherein the processor is further configured to compare the standard deviation of the measurements of the cell granularity parameter for the one or more cells to a reference range.

3. The system of claim 2 , wherein the processor is further configured to characterize the inflammatory response to infection as abnormal if the standard deviation of the measurements of the cell granularity parameter for the one or more cells is outside the reference range.

4. The system of claim 2 , wherein the processor is further configured to identify and measure a volume of monocytes among the heterogenous population of circulating cells passing through the flowcell and calculate a distribution width of the monocyte volume measurements.

5. The system of claim 4 , wherein the processor is further configured to compare the distribution width of the monocyte volume measurements to a second reference range, and to characterize the inflammatory response to infection as abnormal if the standard deviation of the measurements of the cell granularity parameter for the one or more cells is outside reference range and the distribution width of the monocyte volume measurements is outside the second reference range.

6. The system of claim 4 , wherein the processor is further configured to determine a count of white blood cells among the heterogenous population of circulating cells passing through the flow cell.

7. The system of claim 6 , wherein the processor is further configured to:

a. compare the standard deviation of the measurements of the cell granularity parameter for the one or more cells to the reference range;

b. compare the distribution width of the monocyte volume measurements to an second reference range;

C. compare the count of white blood cells to a third reference range; and

d. characterize the inflammatory response to infection based on a combination of at least the standard deviation of the measurements of the cell granularity parameter for the one or more cells, the distribution width of the monocyte volume measurements, and the count of white blood cells.

8. The system of claim 7 , wherein the processor is configured to characterize the inflammatory response to infection as abnormal if the standard deviation of the measurements of the cell granularity parameter for the one or more cells is outside the reference range, the distribution width of the monocyte volume measurements is outside the second reference range and the count of white blood cells is outside the third reference range.

9. The system of claim 7 , wherein the processor is configured to apply local decision rules to characterize the inflammatory response to infection if the standard deviation of the measurements of the cell granularity parameter for the one or more cells, the distribution width of the monocyte volume measurements and the count of white blood cells are not all within or all outside of their respective reference ranges.

10. The system of claim 1 , wherein the one or more cells are classified as non-nucleated red blood cells.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 16, 2023
From: TEJIDOR, LILIANA; MAGARI, ROBERT T.; CAREAGA, DIANA; SHIN, SANGHYUK
To: BECKMAN COULTER, INC.
Reel/Frame 065233/0940 →
Continuity (3)
Division 16925937 · Jul 10, 2020
Provisional Application 62873575 · Jul 12, 2019
Related Publication 20240053253A1 · Feb 15, 2024
References Cited (184)
US 5125737A · Rodriquez et al. · 1992 [cited by applicant]
US 5341291A · Roizen, III et al. · 1994 [cited by applicant]
US 5529933A · Young et al. · 1996 [cited by applicant]
US 6228652B1 · Rodriquez et al. · 2001 [cited by applicant]
US 6509192B1 · Young · 2003 [cited by applicant]
US 7109036B2 · Ortiz et al. · 2006 [cited by applicant]
US 7135341B2 · Ortiz et al. · 2006 [cited by applicant]
US 7176031B2 · Li et al. · 2007 [cited by applicant]
US 7195919B2 · Jacobs et al. · 2007 [cited by applicant]
US 7285417B2 · Ortiz et al. · 2007 [cited by applicant]
US 7390662B2 · Riley et al. · 2008 [cited by applicant]
US 7393688B2 · Ortiz et al. · 2008 [cited by applicant]
US 8094299B2 · Wells et al. · 2012 [cited by applicant]
US 8189187B2 · Graham et al. · 2012 [cited by applicant]
US 8221995B2 · Lee et al. · 2012 [cited by applicant]
US 8719053B2 · Showalter et al. · 2014 [cited by applicant]
US 9939453B2 · Lu et al. · 2018 [cited by applicant]
US 10221453B2 · Shi et al. · 2019 [cited by applicant]
US 20010051879A1 · Johnson et al. · 2001 [cited by applicant]
US 20010051880A1 · Schurenberg et al. · 2001 [cited by applicant]
US 20030105648A1 · Schurenberg et al. · 2003 [cited by applicant]
US 20040042471A1 · Yung et al. · 2004 [cited by applicant]
US 20040220761A1 · Yundt-Pacheco · 2004 [cited by applicant]
US 20040267562A1 · Fuhrer et al. · 2004 [cited by applicant]
US 20050022103A1 · Yundt-Pacheco · 2005 [cited by applicant]
US 20050159982A1 · Showalter et al. · 2005 [cited by applicant]
US 20080186134A1 · Parkhurst et al. · 2008 [cited by applicant]
US 20090149724A1 · Mark et al. · 2009 [cited by applicant]
US 20110046910A1 · Haas et al. · 2011 [cited by applicant]
US 20110076685A1 · Moeller et al. · 2011 [cited by applicant]
US 20110166794A1 · Linssen et al. · 2011 [cited by applicant]
US 20120109531A1 · Knafel et al. · 2012 [cited by applicant]
US 20120109682A1 · Seltzer et al. · 2012 [cited by applicant]
US 20130123131A1 · Purvis et al. · 2013 [cited by applicant]
US 20130197943A1 · Conlin et al. · 2013 [cited by applicant]
US 20130246079A1 · Hoffman et al. · 2013 [cited by applicant]
US 20140148350A1 · Spetzler · 2014 [cited by examiner]
US 20140160464A1 · Han · 2014 [cited by applicant]
US 20140172321A1 · Han · 2014 [cited by applicant]
US 20150338427A1 · Pollack et al. · 2015 [cited by applicant]
US 20160168638A1 · Garrett et al. · 2016 [cited by applicant]
US 20160356801A1 · Glavina et al. · 2016 [cited by applicant]
US 20170248508A1 · Ward et al. · 2017 [cited by applicant]
US 20170285624A1 · Lesher · 2017 [cited by applicant]
US 20170356921A1 · Van Roosmalen et al. · 2017 [cited by applicant]
US 20180305758A1 · Shi et al. · 2018 [cited by applicant]
US 20190128906A1 · Ramirez et al. · 2019 [cited by applicant]
US 20190170749A1 · Anderson · 2019 [cited by examiner]
US 20190324035A1 · Magari et al. · 2019 [cited by applicant]
US 20190324036A1 · Xin et al. · 2019 [cited by applicant]
US 20190348182A1 · Magari et al. · 2019 [cited by applicant]
US 20190383800A1 · Careaga et al. · 2019 [cited by applicant]
US 20200243171A1 · Schmidt · 2020 [cited by applicant]
US 20200253562A1 · Newberry · 2020 [cited by examiner]
US 20200253564A1 · Barak et al. · 2020 [cited by applicant]
US 20210007675A1 · Tejidor et al. · 2021 [cited by applicant]
US 20210010924A1 · Tejidor et al. · 2021 [cited by applicant]
US 20210011005A1 · Tejidor et al. · 2021 [cited by applicant]
US 20210059597A1 · Chung · 2021 [cited by examiner]
US 20210303818A1 · Randolph et al. · 2021 [cited by applicant]
US 20230005566A1 · Xin et al. · 2023 [cited by applicant]
CN 102033035B · 2013 [cited by applicant]
EP 1021701 · 2000 [cited by applicant]
EP 1718966 · 2006 [cited by applicant]
JP 2012529033A · 2012 [cited by applicant]
KR 20150036329A · 2015 [cited by applicant]
KR 20150091049A · 2015 [cited by applicant]
WO WO2004044556A2 · 2004 [cited by applicant]
WO WO2012139047A2 · 2012 [cited by applicant]
WO WO2014028534A2 · 2014 [cited by applicant]
WO WO2014084930A1 · 2014 [cited by applicant]
WO WO2014154810A1 · 2014 [cited by applicant]
WO WO2017132132A1 · 2017 [cited by applicant]
Abiramalatha, T., et al. “Utility of neutrophil volume conductivity scatter (VCS) parameter changes as sepsis screen in Neonates. ”Journal of Perinatoloty 36.9 (2016): 733-738. [cited by applicant]
Aird, William C., “The Hematologic System as a Marker of Organ Dysfunction in Sepsis”, Mayo Clin Proc., Jul. 2003;78:869-881, 2003 Mayo Foundation for Medical Education and Research. [cited by applicant]
Anonymous, “Multiple Logistic Regression Analysis”, Jan. 17, 2013, retrieved from http://sphweb.bumc.cu.edu/otlt/MPH-Modules/8S/8S704_Multivariable/8S704_Multivariables8.html. [cited by applicant]
Beckman Coulter, “Coulter® 3-D VCS Technology,” from <http://www.cyto.purdue.edu/cdroms/cyto2/6/coulter/ ss000125.htnn> (Year: 1996). [cited by applicant]
Beckman Coulter, Early Sepsis Indicator (ESId) Application for UniCel DxH 900 Series with System Manager Software, PN C26693AC (Jun. 2019), <https://www.beckmancoulter.corn/download/file/wsr-308328/C26693AC?type=pdf> (Y… [cited by applicant]
Beckman Coulter, Early Sepsis Indicator (ESId) Application Addendum, UniCel DxH 900 Series with System Manager Software Coulter Cellular Analysis System, Pn C42014AC (Apr. 2020), <https://www.beckmancoulter.com/download… [cited by applicant]
Beckman Coulter, UniCel DxH 900 Series with System Manager Software, PN B26647AG, <https:// www.beckmancoulter.corn/download/file/wsr-156667/B26647AG?type=pdf> (Year: 2020). [cited by applicant]
Bhargava, et al. “Elevated mean neutrophil volume+ CRP is a highly sensitive and specific predictor of neonatal sepsis”, Letter to the Editor, International Journal of Laboratory Hematology, DOI: 10.1111/iijh.12120, 201… [cited by applicant]
“Biomarker” The Pharmaceutical Society of Japan, a pharmaceutical science glossary, 2008, 2 pgs. [cited by applicant]
Celik, et al., “Automated determination of neutrophil VCS parameters in diagnosis and treatment efficacy of neonatal sepsis”, Pediatric Research, vol. 71, No. 1, Jan. 2012, pp. 121-125. [cited by applicant]
Cembrowski, George S., B. Smith, and D. Tung. “Rationale for using insensitive quality control rules for today's hematology analyzers.” [cited by applicant]
Chaves, et al. “Neutrophil Volume Distribution Width: A New Automated Hematologic Parameter for Acute Infection”, Arch Pathol Lab Med, vol. 130. Mar. 2006, pp. 378-380. [cited by applicant]
Chaves, et al. Quantitative Determination of Neutrophil VCS Parameters by the Coulter Automated Hematology Analyzer: New and Reliable Indicators for Acute Bacterial Infection. American Journal Clinical Pathology, 2005, … [cited by applicant]
Chen, Hong-Jhang, et al. “Study on Yang-Xi Using Body Constitution Questionnaire and Blood Variables in healthy Volunteer.” Evidence—Based Complementary and Alternative Medicine 2016 (2016). [cited by applicant]
Cho, et al., “Biomarkers of Sepsis”, Infection & Chemotherapy, Feb. 2014; 46:1-12. [cited by applicant]
Crouser, et al., “Improved Early Detection of Sepsis in the ED with a Novel Monocyte Distribution Width Biomarker”, 152#3 Chest, Sep. 2017, pp. 518-526. [cited by applicant]
Dellinger, et al. “Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012”, Intensive Care Medicine, 2013, 39:164-228. [cited by applicant]
Dilmoula, et al., “Volume, Conductivity and Scatter Properties of Leukocytes (VCS Technology) in Detecting Sepsis in Critically III Adult Patients”, Blood (ASH annual Meeting Abstracts) 2011; 118: Abstract 4729, 3 pages. [cited by applicant]
Early Sepsis Indicator Application Addendum UniCel DxH 900 Coulter Cellular Analysis System, Beckman Coulter, published Version: v1, Available online at: https://www.analis.be/site/objects/media/0/0/8/1/9/0081990_media/… [cited by applicant]
Ferrer, et al., “Emperic Antibiotic Treatment Reduces Mortality in Severe Sepsis and Septic Shock from the First Hour: Results from a Guideline-Based Performance Improvement Program”, Critical Care Medicine, Aug. 2014, … [cited by applicant]
FDA 510(k) Substantial Equivalence Determination Decision Summary, <https://www.accessdata.fda.gov/cdrh_docs /reviews/K181599.pdf> (Year: 2018). [cited by applicant]
Gaieski, et al., “Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department”, Critical Care Medicine, 2010, vo… [cited by applicant]
Garnacho-Montero, et al., “Impact of adequate empirical antibiotic therapy on the outcome of patients admitted to the intensive care unit with sepsis”, Critical Care Medicine, 2003;31 :2742-51. [cited by applicant]
Gea-Banecloche, et al. “Sepsis associated with immunosuppressive medications: An evidence-based review” Critical Care Medicine 2004; 32:S578-S590. [cited by applicant]
Glickman, et al., Disease Progression in Hemodynamically Stable Patients Presenting to the Emergency Department with Sepsis. Academic Emergency Medicine, vol. 17, Issue 4, Apr. 2, 2010, pp. 383-390. [cited by applicant]
Goyette, et al., “Hematologic changes in sepsis and their therapeutic implications,” Seminars in Respiratory and Critical Care Medicine, vol. 25, No. 6, pp. 645-659 (2004). [cited by applicant]
Hou, et al., Viral infection triggers rapid differentiation of human blood monocytes into dendritic cells, Blood, Mar. 29, 2012, vol. 119, No. 12, pp. 3128-3132. [cited by applicant]
Kaukonen, et al., “Systemic Inflammatory Response Syndrome Criteria in Defining Severe Sepsis,” New England Journal of Medicine, 372: 1629-38, Apr. 23, 2015, (doi:610.1056/NEJMoal415236). [cited by applicant]
Lee, et al., “Mean cell vols. of neutrophils and monocytes are promising markers of sepsis in elderly patients”, Blood Research, vol. 48, No. 3, Sep. 2013, 5 pages. [cited by applicant]
Levy, et al., “2001 SCCM/ESICM/ACCP/ATS/SIS Sepsis Definitions Conference”, Critical Care Medicine, Mar. 28, 2003, 29: 530-538. [cited by applicant]
Liu, et al., “Hospital Deaths in Patients with Sepsis from 2 Independent Cohorts”, JAMA Jul. 2, 2014; 312: 90-92. [cited by applicant]
Mardi, et al., Mean cell volume of neutrophils and monocytes compared with C-reactive protein, interleukin-6 and white blood cell count for prediction of sepsis and nonsystemic bacterial infections, accepted for publica… [cited by applicant]
Nachimuthu, Senthil K., and Peter J. Haug. “Early detection of sepsis in the emergency department using Dynamic Bayesian Networks.” [cited by applicant]
Petrak, Russel M., et al. “The value of an infectious diseases specialist.” [cited by applicant]
Park, et al., “Screening of sepsis using leukocyte cell population data from the Coulter automatic blood cell analyzer DxH800”, International Journal of Laboratory Hematology, Dec. 6, 2010, 9 pages. [cited by applicant]
Raimondi, et al., “Automated Determination of Neutrophil Volume as Screening Test for Late-Onset Sepsis in Very Low Birth Infants”, Pediatric Infectious Disease Journal, Feb. 2010; 29:288-89. [cited by applicant]
“Red Blood Cell Distribution With (RDW): Definition and Calculation—LabCE.com, Laboratory Continuing Education,” Nov. 2012, downloaded Aug. 22, 2019 from: https://labce.com/spg579122_red_blood_cell_distribution_width_rd… [cited by applicant]
Seymour, et al. “Severe Sepsis in Pre-Hospital Emergency Care: Analysis of Incidence, Care, and Outcome”, American Journal of Respiratory Critical Care Medicine, Dec. 15, 2012; 186:1264-71. [cited by applicant]
Shalova, et al., “Human Monocytes Undergo Functional Re-programming during Sepsis Mediated by Hypozia-Inducible Factor-1a”, Immunity, Mar. 17, 2015; 42:484-98. [cited by applicant]
Singer, et al., “The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3),” JAMA, 10 315(8): 801-810, Feb. 23, 2016. [cited by applicant]
Skibsted, et al., “Bench-to-bedside review: Future novel diagnostics for sepsis—a systems biology approach”, Critical Care Oct. 4, 2013; 17:231, 15 pages. [cited by applicant]
Sukhacheva, et al., “The Role of Monocytes in the Progression of Sepsis,” Beckman Coulter, 2018, downloaded Aug. 22, 2019 from: media.beckmancoulter.com/-/media/diagnostics/products/hematology/early-sepsis-indicator/doc… [cited by applicant]
Torio, et al., “National Inpatient Hospital Costs: The Most Expensive Conditions by Payer, 2011”, H-Cup US, Aug. 2013, 8 pages, retrieved from: https://www.hcup-us.ahrq.gov/reports/statbriefs/sb160.jsp. [cited by applicant]
“UniCel DxH 800—Coulter Cellular Analysis System”, Available online at: https://www.udh.med.sa/advices/DxH_operator_Manual.pdf, Aug. 5, 2017, 54 pages. [cited by applicant]
Vis, et al., “Verification and Quality Control of Routine Hematology Analyzers”, International Journal of Laboratory Hematology, vol. 38, No. 1, May 9, 2016, pp. 100-109. [cited by applicant]
Warner, “Tips for evaluating a peripheral blood smear for possible sepsis,” Jan. 15, 2013, 3 pages, available at laboratorian.advanceweb.com/signs-of-sepsis/. [cited by applicant]
Zhou, et al., “VCS parameters of neutrophils, monocytes and lymphocytes may indicate local bacterial infection in cancer patients who accepted cytotoxic chemotherapeutics,” Eur J Clin Microbiol Infect Dis, 2016, 35:41-4… [cited by applicant]
Zonneveld, R., et al., “Analyzing Neutrophil Morphology, Mechanics, and Motility in Sepsis: Options and Challenges for Novel Bedside Technologies,” Crit Care Med, 2016, 44(1):218-228, 11 pgs. [cited by applicant]
Chinese Office Action dated Feb. 16, 2023 for Application No. 201880076679.9, 3 pages. [cited by applicant]
European Examination Report dated Oct. 15, 2020 for Application No. EP 17704357.7, 10 pgs. [cited by applicant]
European Examination Report dated Jul. 12, 2022, for Application No. 18845383.1, 13 pages. [cited by applicant]
European Examination Report dated Jan. 25, 2023 for Application No. EP 19728159., 5 pages. [cited by applicant]
Indian Office Action dated Jun. 25, 2021, for Application No. 201817031635, 7 pages. [cited by applicant]
International Search Report and Written Opinion dated Apr. 20, 2017 for International Application No. PCT/US2017/014708, 16 pages. [cited by applicant]
International Search Report and Written Opinion dated May 4, 2018 for International Application No. PCT/US2018/020087, 13 pages. [cited by applicant]
International Search Report and Written Opinion dated Mar. 26, 2019 for International Application No. PCT/US2018/057645, 16 pages. [cited by applicant]
International Search Report and Written Opinion dated Sep. 4, 2019 for International Application No. PCT/US2019/028486, 11 pgs. [cited by applicant]
International Search Report and Written Opinion dated Aug. 2, 2019 for International Application No. PCT/US2019/028487, 7 pages. [cited by applicant]
International Search Report and Written Opinion dated Aug. 23, 2019 for International Application No. PCT/US2019/028488, 10 pgs. [cited by applicant]
International Search Report and Written Opinion dated Aug. 20, 2019 for International Application No. PCT/US2019/031151, 9 pages. [cited by applicant]
International Search Report and Written Opinion dated Oct. 20, 2020 for International Application No. PCT/US2020/041535, 12 pgs. [cited by applicant]
International Search Report and Written Opinion dated Oct. 8, 2020 for International Application No. PCT/US2020/041548, 10 pgs. [cited by applicant]
International Search Report and Written Opinion dated Oct. 5, 2020 for International Application No. PCT/US2020/041541, 10 pgs. [cited by applicant]
Japanese Office Action, Notice of Reasons for Refusal, dated Jan. 30, 2023 for JP 2022-076469, 1 page. [cited by applicant]
Japanese Office Action, Notice of Reasons for Refusal, dated Oct. 29, 2020 JP 2018-538892, 27 pgs. [cited by applicant]
Japanese Notification of Reasons for Refusal dated Feb. 4, 2022, for Application No. 2021-012832, 4 pages. [cited by applicant]
Japanese Notification of Reasons for Refusal dated Jun. 17, 2022, for Application No. 2021-012832, 2 pages. [cited by applicant]
Korean Office Action dated Mar. 20, 2023 for KR 10-2022-7020710, 23 pages. [cited by applicant]
Korean Office Action dated Aug. 27, 2021, for Application No. 10-2018-7024386, 27 pages. [cited by applicant]
US Office Action, Final Rejection dated Nov. 29, 2022 for U.S. Appl. No. 16/170,389, 22 pages. [cited by applicant]
US Office Action, Final Rejection dated Nov. 28, 2022 for U.S. Appl. No. 16/390,597, 9 pages. [cited by applicant]
US Office Action, Non-Final Rejection, dated Jan. 19, 2023 for U.S. Appl. No. 16/925,943, 20 pages. [cited by applicant]
US Office Action, Non-Final Rejection, dated Jan. 19, 2023 for U.S. Appl. No. 17/391,599, 34 pages. [cited by applicant]
US Office Action, Final Rejection, dated Mar. 3, 2023 for U.S. Appl. No. 16/925,933, 11 pages. [cited by applicant]
US Office Action, Non-Final Rejection, dated Mar. 14, 2023 for U.S. Appl. No. 16/170,389, 9 pages. [cited by applicant]
US Office Action, Restriction Requirement, dated Apr. 7, 2021 for U.S. Appl. No. 15/987,541, 5 pgs. [cited by applicant]
US Office Action, Non-Final Rejection, dated Jul. 31, 2020 for U.S. Appl. No. 16/073,757, 23 pgs. [cited by applicant]
US Office Action, Notice of Allowance, dated Feb. 8, 2021 for U.S. Appl. No. 16/073,757, 20 pgs. [cited by applicant]
US Non-Final Rejection dated Jul. 9, 2021, for U.S. Appl. No. 15/987,541, 15 pages. [cited by applicant]
US Final Rejection dated Feb. 17, 2022, for U.S. Appl. No. 15/987,541, 14 pages. [cited by applicant]
US Notice of Allowance dated Sep. 1, 2022, for U.S. Appl. No. 15/987,541, 8 pages. [cited by applicant]
US Restriction Requirement dated May 2, 2022, for U.S. Appl. No. 16/170,389, 7 pages. [cited by applicant]
US Non-Final Rejection dated Aug. 1, 2022, for U.S. Appl. No. 16/170,389, 21 pages. [cited by applicant]
US Restriction Requirement dated Mar. 14, 2022, for U.S. Appl. No. 16/390,597, 6 pages. [cited by applicant]
US Non-Final Rejection dated Jun. 13, 2022, for U.S. Appl. No. 16/390,597, 8 pages. [cited by applicant]
US Non-Final Rejection dated Jul. 2, 2021, for U.S. Appl. No. 16/390,633, 9 pages. [cited by applicant]
US Non-Final Rejection dated Feb. 25, 2022, for U.S. Appl. No. 16/390,633, 13 pages. [cited by applicant]
US Final Rejection dated Aug. 9, 2022, for U.S. Appl. No. 16/390,633, 11 pages. [cited by applicant]
US Non-Final Rejection dated Jul. 9, 2021, for U.S. Appl. No. 16/390,648, 15 pages. [cited by applicant]
US Final Rejection dated Feb. 17, 2022, for U.S. Appl. No. 16/390,648, 14 pages. [cited by applicant]
US Notice of Allowance dated Jun. 15, 2022, for U.S. Appl. No. 16/390,648, 7 pages. [cited by applicant]
US Restriction Requirement dated Jun. 16, 2021, for U.S. Appl. No. 16/488,503, 8 pages. [cited by applicant]
US Non-Final Rejection dated Nov. 24, 2021, for U.S. Appl. No. 16/488,503, 21 pages. [cited by applicant]
US Final Rejection dated Aug. 11, 2022, for U.S. Appl. No. 16/488,503, 21 pages. [cited by applicant]
US Non-Final Rejection dated Jun. 23, 2022, for U.S. Appl. No. 16/925,933, 9 pages. [cited by applicant]
US Restriction Requirement dated Oct. 5, 2022, for U.S. Appl. No. 16/925,943, 8 pages. [cited by applicant]
Bruscia, Emanuela M., et al. “Abnormal trafficking and degradation of TLR4 underlie the elevated inflammatory response in cystic fibrosis.” [cited by applicant]
Kirkpatrick, Brian, and Brian J. Miller. “Inflammation and schizophrenia.” [cited by applicant]
Lin, Yaojin, et al. “Synthesizing decision rules from multiple information sources: A neighborhood granulation viewpoint.” [cited by applicant]
Purohit, Abhishek HL, et al. “Volume conductivity, and scatter parameters as diagnostic aid to bacterial sepsis: A tertiary care experience.” [cited by applicant]
Suresh, Pooja K., et al. “Volume conductivity and scatter parameters as an indicator of acute bacterial infections by the automated haematology analyser. ” [cited by applicant]
European Examination Report dated Jan. 2, 2024, for Application No. 23197126.8, 10 pages. [cited by applicant]
Japanese Notification of Reasons for Refusal dated Apr. 8, 2024, for Application No. 2022-500896, 6 pages. [cited by applicant]
Korean Final Office Action dated Oct. 20, 2023, for Application No. 10-2022-7020710, 6 pages. [cited by applicant]
US Notice of Allowance dated Jan. 24, 2024, for U.S. Appl. No. 16/390,597, 9 pages. [cited by applicant]
US Non-Final Office Action dated Nov. 3, 2023, for U.S. Appl. No. 16/925,933, 14 pages. [cited by applicant]
US Notice of Allowance dated Feb. 23, 2024, for U.S. Appl. No. 16/925,933, 8 pages. [cited by applicant]
US Non-Final Office Action dated Jul. 11, 2023, for U.S. Appl. No. 16/925,943, 31 pages. [cited by applicant]
US Non-Final Office Action dated Mar. 7, 2024, for U.S. Appl. No. 16/925,943, 40 pages. [cited by applicant]
US Final Office Action dated Aug. 3, 2023, for U.S. Appl. No. 17/391,599, 32 pages. [cited by applicant]
US Notice of Allowance dated Apr. 5, 2024, for U.S. Appl. No. 17/391,599, 13 pages. [cited by applicant]