METHOD FOR DETECTING CIRCULATING CELLS IN SUPERFICIAL BODY FLUIDS

• US 20180263602A1
• Filed: 09/19/2016
• Published: 09/20/2018
• Est. Priority Date: 09/17/2015
• Status: Active Grant

• Current Assignee: Consejo Superior de Investigaciones Científicas,, Fundación para el Conocimiento madri+d, Massachusetts Institute of Technology
• Original Assignee: Consejo Superior de Investigaciones Científicas,, Fundación para el Conocimiento madri+d, Massachusetts Institute of Technology
• Inventors: ELVIRA SEGURO, Luis, MARTINEZ GRAULLERA, Oscar, KANT SHUKLA, Shiva, MONTERO, Francisco, JIMENEZ, Javier, BUTTERWORTH, Ian Richard, ANTHONY, Brian, HEASON LEE, John, CASTRO GONZALEZ, Carlos
• Granted Patent: US 10,639,012 B2
• Time in Patent Office: Days
• CPC Class Codes: A61B 8/0891 for diagnosis of blood vessels
• CPC Class Codes: A61B 8/5223 for extracting a diagnostic or physiological parameter from medical diagnostic data for algorithms to analyse biomedical images G06T7/0012
• CPC Class Codes: A61B 8/58 Testing, adjusting or calibrating the diagnostic device
• CPC Class Codes: G01N 15/02 Investigating particle size or size distribution by measuring osmotic pressure G01N7/10; investigating sedimentation of particle suspensions G01N15/04; investigating individual particles G01N15/10
• CPC Class Codes: G01N 15/0211 Investigating a scatter or diffraction pattern
• CPC Class Codes: G01N 15/1023 Microstructural devices for non-optical measurement
• CPC Class Codes: G01N 2015/0687 in solutions, e.g. non volatile residue
• CPC Class Codes: G01N 2015/1006 for cytology
• CPC Class Codes: G01N 2015/1027 Determining speed or velocity of a particle
• CPC Class Codes: G01N 2015/1029 Particle size
• CPC Class Codes: G01N 2291/02466 Biological material, e.g. blood
• CPC Class Codes: G01N 29/02 Analysing fluids using acoustic emission techniques G01N29/14 ; constructional or flow details for analysing fluids G01N29/222; optoacoustic fluid cells G01N29/2425
• CPC Class Codes: G01N 29/032 by measuring attenuation of acoustic waves
• CPC Class Codes: G16H 50/30 for calculating health indices; for individual health risk assessment
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Abstract

The present invention relates to a method for measuring circulating cells in superficial body fluids by means of high-frequency-based device. The method can be used for detecting circulating cells in the fluids of an individual without the necessity of extracting a sample of the individual, being useful as a diagnostic tool and for monitoring the effectiveness of a treatment administered to an individual suffering from a viral, protozoal, fungal and/or bacterial disease.

Claims

1. An in vitro use of an ultrasound-based device for detecting and quantifying circulating cells in superficial body fluids of a subject, for the diagnosis of viral, protozoal, fungal and/or bacterial disease in a subject, for identifying subjects who may be suffering from a viral, protozoal, fungal and/or bacterial disease, or for monitoring the effectiveness of a treatment administered to a subject suffering from a viral, protozoal, fungal and/or bacterial disease, wherein the ultrasound-based device operates at a central frequency in the range of 10-100 MHz and at a pulse duration between 25-1,000 ns, and at a wavelengths between 15 and 150 μ

m.

2. In vitro use according to claim 1, wherein the signal emitted by the ultrasound-based device operates at a central frequency of 20 MHz and/or at a pulse duration of 500 ns, and/or at a wavelength of 75 μ

m.

3. In vitro use according to claim 1 or 2, wherein the circulating cells are white blood cells, red blood cells or cancer cells.

4. In vitro use according to any of claims 1 to 3, wherein the ultrasound-based device comprises a transducer.

5. In vitro use according to any of claims 1 to 4, wherein the superficial body fluid is selected from the group consisting of cerebrospinal fluid, blood, urine, pleural fluid, synovial fluid and pericardial fluid.

6. In vitro use according to any of claims 1 to 5, wherein the viral, protozoal, fungal and/or bacterial disease is meningitis.

7. An in vitro method for detecting and quantifying circulating cells in superficial body fluids of a subject comprising

a) placing an ultrasound-based device in contact with a liquid sample isolated from a superficial body fluid of the subject for obtaining a ultrasound data of said liquid sample;

b) analyzing the ultrasound data obtained in step a) by a data processing system which provides information about cells and their concentration in the fluid, and

c) correlating the information obtained in step b) with the presence and amount of circulating cells in the individual,

wherein the ultrasound-based device operates at a central frequency in the range of 10-100 MHz and at a pulse duration between 25-1,000 ns, and at a wavelengths between 15 and 150 μ

m.

8. Method according to claim 7, wherein the signal emitted by the ultrasound-based device operates at a central frequency of 20 MHz and/or at a pulse duration of 500 ns, and/or at a wavelength of 75 μ

m.

9. Method according to claim 7 or 8, wherein the circulating cells are white blood cells, red blood cells or cancer cells.

10. Method according to any of claims 7 to 9, wherein the ultrasound-based device comprises a transducer.

11. Method according to any of claims 7 to 10, wherein the ultrasound data obtained in step a) is in the form of (i) collection of A-line data and/or of (ii) B-mode or C-mode type of 2D data or 3D data.

12. Method according to any of claims 7 to 11, wherein the data processing system comprises an algorithm.

13. Method according to any of claims 7 to 12, wherein the information about cells is cell size, cell concentration and/or cell viability.

14. Method according to any of claims 7 to 13, wherein the superficial body fluid is selected from the group consisting of cerebrospinal fluid, blood, urine, pleural fluid, synovial fluid and pericardial fluid.

15. An in vitro method for the diagnosis of a viral, protozoal, fungal and/or bacterial disease in a subject or for identifying subjects who may be suffering from a viral, protozoal, fungal and/or bacterial disease comprising

a) quantifying circulating cells in superficial body fluids of the subject by a method according to any of claims 7 to 14, and

b) correlating the amount of said circulating cells with the presence of a viral, protozoal, fungal and/or bacterial disease in the subject, wherein an amount of circulating cells higher than a reference value is indicative of a viral, protozoal, fungal and/or bacterial disease, or is indicative that the subject may be suffering from a viral, protozoal, fungal and/or bacterial disease.

16. An in vitro method for monitoring the effectiveness of a treatment administered to a subject suffering from a viral, protozoal, fungal and/or bacterial disease, comprising

a) quantifying circulating cells in a superficial body fluid of the subject before and after the treatment by a method according to any of claims 7 to 14, and

b) correlating the amount of said circulating cells with the effectiveness of the treatment administered to said subject,

wherein an amount of circulating cells in the subject after the treatment lower than the amount of circulating cells before the treatment is indicative that the treatment is being effective.

17. An in vitro method according to claim 15 or 16, wherein the viral, protozoal, fungal and/or bacterial disease is meningitis.

18. A non-invasive use of an ultrasound-based device for detecting and quantifying circulating cells in superficial body fluids of a subject, for the diagnosis of viral, protozoal, fungal and/or bacterial disease in a subject, for identifying subjects who may be suffering from a viral, protozoal, fungal and/or bacterial disease or for monitoring the effectiveness of a treatment administered to a subject suffering from a viral, protozoal, fungal and/or bacterial disease, wherein the ultrasound-based device operates at a central frequency in the range of 10-50 MHz, and at a pulse duration between 50-1,000 ns, and at a wavelength between 30 and 150 μ

m.

19. Non-invasive use according to claim 18, wherein the signal emitted by the ultrasound-based device operates at a central frequency of 20 MHz and/or at a pulse duration of 500 ns, and/or at a wavelength of 75 μ

m.

20. Non-invasive use according to claim 18 or 19, wherein the circulating cells are white blood cells, red blood cells or cancer cells.

21. Non-invasive use according to any of claims 18 to 20, wherein the superficial body fluid is selected from the group consisting of cerebrospinal fluid, blood, urine, pleural fluid, synovial fluid and pericardial fluid.

22. Non-invasive use according to any of claims 18 to 21, wherein the viral, protozoal, fungal and/or bacterial disease is meningitis.

23. A non-invasive method for detecting and quantifying circulating cells in superficial body fluids comprising

a) placing an ultrasound-based device on the skin of the subject for obtaining a ultrasound data of the a superficial body fluid under the skin;

b) analyzing the ultrasound data obtained in step a) by a data processing system which provides information about cells and their concentration in the fluid, and

c) correlating the information obtained in step b) with the presence and amount of circulating cells in the subject,

wherein the ultrasound-based device operates at a central frequency in the range of 10-50 MHz, and at a pulse duration between 50-1,000 ns, and at a wavelength between 30 and 150 μ

m.

24. Method according to claim 23, wherein the signal emitted by the ultrasound-based device operates at a central frequency of 20 MHz and/or at a pulse duration of 500 ns, and/or at a wavelength of 75 μ

m.

25. Method according to claim 23 or 24, wherein the circulating cells are white blood cells, red blood cells or cancer cells.

26. Method according to any of claims 23 to 25, wherein the ultrasound-based device comprises a transducer.

27. Method according to any of claims 23 to 26, wherein the ultrasound data obtained in step a) is in the form of (i) collection of A-line data and/or of (ii) B-mode or C-mode type of 2D data or 3D data.

28. Method according to any of claims 23 to 27, wherein the data processing system comprises an algorithm.

29. Method according to any of claims 23 to 28, wherein the information about cells is cell size, cell concentration and/or cell viability.

30. Method according to any of claims 23 to 29, wherein the superficial body fluid is selected from the group consisting of cerebrospinal fluid, blood, urine, pleural fluid, synovial fluid and pericardial fluid.

31. A method for the diagnosis of a viral, protozoal, fungal and/or bacterial disease in a subject or for identifying subjects who may be suffering from a viral, protozoal, fungal and/or bacterial disease, comprising

a) quantifying circulating cells in superficial body fluids of the subject by a method according to any of claims 23 to 30, and

b) correlating the amount of said circulating cells with the presence of a viral, protozoal, fungal and/or bacterial disease in the subject, wherein an amount of circulating cells higher than a reference value is indicative of a viral, protozoal, fungal and/or bacterial disease, is indicative that the subject may be suffering from a viral, protozoal, fungal and/or bacterial disease.

32. Method for monitoring the effectiveness of a treatment administered to a subject suffering from a viral, protozoal, fungal and/or bacterial disease comprising

a) quantifying circulating cells in a superficial body fluid of the subject before and after the treatment by a method according to any of claims 23 to 30, and

b) correlating the detection of said circulating cells with the effectiveness of the treatment administered to said subject,

wherein an amount of circulating cells in the subject after the treatment lower than the amount of circulating cells before the treatment is indicative that the treatment is being effective.

33. Method according to claim 31 or 32, wherein the viral, protozoal, fungal and/or bacterial disease is meningitis.