System and method for time-related microscopy of biological organisms

Patent metadata

Field	Value
Publication number	US-9915813-B2
Application number	US-201013513500-A
Country	US
Kind code	B2
Filing date	Dec 1, 2010
Priority date	Dec 4, 2009
Publication date	Mar 13, 2018
Grant date	Mar 13, 2018

Abstract

The invention relates to a system and a method for determination of a value for at least one parameter describing microbial activity of individual biological organisms in a liquid sample. Images, wherein individual biological organisms may be identified, are combined to provide optical sectionings of the biological organisms and the optical sectionings are analyzed to determine the value for said at least one parameter describing microbial activity of said individual biological organisms in each sample container.

First claim

The invention claimed is:

1. A system for determination of a value for at least one parameter describing microbial activity of individual biological organisms in a liquid sample comprising a plurality of biological organisms, said system comprising:
an option detection assembly comprising at least one image acquisition device adapted to acquire images wherein individual biological organisms may be identified,
at least one sample device comprising at least one sample container for holding the sample in liquid form,
at least one translating unit arranged to move said liquid sample device and said optical detection assembly relative to each other,
a control unit for controlling said optical detection assembly and said translating unit, said control unit is adapted to sequentially acquire optical sectionings from said liquid sample comprising at least a first and a second optical sectioning of the same biological organisms in said liquid sample, each of the optical sectionings comprises several images of the plurality of biological organisms, and there being a first time interval between acquisitions of said at least first and second optical sectioning,
an image analysing device for analysing said images of said first and said second optical sectionings wherein said image analysing device comprises algorithms adapted to determine said value for said at least one parameter describing microbial activity of said individual biological organisms in each sample container.

2. The system according to claim 1 , wherein said optical detection assembly further comprises an image illumination device.

3. The system according to claim 2 , wherein said image illumination device comprises a light source selected from a laser, a diode laser, a LED, a light bulb, a white light source or a polarized light source.

4. The system according to claim 1 further comprising a stimulating device for providing stimulation to said sample in said sample device.

5. The system according to claim 4 , wherein said stimulation comprises applying an electromagnetic field, a magnetic field, an electric field or an acoustic wave.

6. The system according to claim 1 , further comprising a liquid sample environment controlling device adapted to control at least one of a physical environment of said biological organisms in said liquid sample, and a chemical environment of said liquid sample.

7. The system according to claim 6 , wherein said liquid sample environment controlling device is adapted to control temperature of said liquid sample.

8. The system according to claim 6 , wherein said liquid sample environment controlling device is adapted to control at least pH value, level of nutrition, partial pressure of gasses, salinity, level of alkali metal ions or level of alkaline earth metals.

9. The system according to claim 1 , wherein said parameter is selected from a group of cell division rate, cell viability, living/dead rate, Brownian movements, metabolic rate, morphology, growth factor, kinetics and focus behaviour.

10. The system according to claim 1 , wherein said microbial activity comprises the microbial susceptibility of said biological organisms toward an antibiotic agent.

11. The system according to claim 1 , wherein the number of sample containers N cont on sample device equals 2, 3, 4, 5, 6, 8, 9, 10, 12, 14, 15, 16, 18, 20, 21, 22, 24, 25, 26, 27, 28, 30, or more than 30.

12. The system according to claim 1 , wherein at least a part of said sample containers are inoculated with a first agent.

13. The system according to claim 12 , wherein at least a part of said sample containers are inoculated with N agent different agents, where N agent is 2, 3, 4, 5, 6, 8, 10, 20, or more than 20.

14. The system according to claim 1 , wherein said control unit is adapted to acquire optical sectionings from each sample container over a period of time.

15. The system according to claim 14 , wherein said period of time is below 144 hours.

16. The system according to claim 14 , wherein said period of time is below 2700 seconds.

17. The system according to claim 14 , wherein said control unit is adapted to change said period of time depending on said determined value of said parameter.

18. The system according to claim 1 , wherein said control unit is adapted to sequentially acquire optical sectionings from at least two different sample containers with a first time interval between the acquisition of following two optical sectionings.

19. The system according to claim 1 , wherein said control unit is adapted to sequentially acquire optical sectionings from a sample container with a second time interval between two subsequent sectionings from a sample container.

20. The system according to claim 18 , wherein said control unit is adapted to change said first time interval depending on said determined value of said parameter.

21. The system according to claim 19 , wherein said f control unit is adapted to change said second time interval depending on said determined value of said parameter.

22. The system according to claim 1 , wherein said control unit is adapted to stop image acquisition when said value of said parameter satisfies a predetermined condition.

23. The system according to claim 22 , wherein said predetermined condition is related to the determination of antibiotic susceptibility of said biological organisms or to the determination of minimum inhibitory concentration (MIT).

24. A method for determining of microbial activity in a liquid sample comprising a plurality of biological organisms, said method comprising
sequentially acquiring a plurality of optical sectionings of said liquid sample that comprises a plurality of biological organisms, each of the optical sectionings comprises several images of the same plurality of biological organisms, and each optical sectioning is taken at a different point in time,
selecting a first and a second optical sectioning from said plurality of sectionings, there being a first time interval between the acquisitions of said at least first and section optical sectioning,
computing a value of at least one parameter for each optical sectioning,
determining if a change in said value of said at least one parameter has occurred between said first and second optical sectionings, and
determining said microbial activity in said liquid sample from said change in said value of said at least one parameter.

25. The method according to claim 24 , wherein said microbial activity is related to biological organisms selected from bacteria, archaea, yeast, fungi, pollen, viruses, leukocytes, such as granulocytes, monocytes, Erythrocytes, Thrombocytes, oocytes, sperm, zygote, or stem cells.

26. The method according to claim 24 , wherein said microbial activity is related to biological organisms comprised in clinical material selected from faeces, swap samples from skin, lesions, serosal or mucosal surfaces, urine, lymph, pus, expectorate, transudate, exudates, glandular excretions such as milk, sweat, saliva, tear fluid, sebaceous discharge, nasal or other mucosal discharge, blood, cerebrospinal fluid, timorous tissue, biopsies material from any tissue, extracellular fluid, serum or plasma.

27. The method according to claim 24 , wherein said liquid sample is comprised in at least one sample container.

28. The method according to claim 27 , wherein optical sectionings are acqui

Assignees

• Olesen Tom
• Valvik Martin Christian
• Larsen Niels Agersnap
• Koninklijke Philips Nv

Inventors

• Olesen Tom
• Valvik Martin Christian
• Larsen Niels Agersnap

Classifications

• G02B21/0004 Primary

  specially adapted for specific applications · CPC title

• C12Q1/18

  Testing for antimicrobial activity of a material · CPC title

• G02B21/365

  Control or image processing arrangements for digital or video microscopes (G02B21/361, G02B21/362 take precedence) · CPC title

• G01B9/04

  Measuring microscopes · CPC title

• G02B21/36 Primary

  arranged for photographic purposes or projection purposes (G02B21/18 takes precedence){or digital imaging or video purposes including associated control and data processing arrangements (image data processing per se G06T)} · CPC title