Device and method for analyzing biological objects with Raman spectroscopy

• US 10,545,091 B2
• Filed: 11/23/2016
• Issued: 01/28/2020
• Est. Priority Date: 11/23/2015
• Status: Active Grant

• Current Assignee: Microphotonx GmbH
• Original Assignee: CellTool GmbH
• Inventors: Schutze, Karin, Schutze, Raimund
• Primary Examiner(s): Nur, Abdullahi
• Application Number:
  US15/778,116
• Publication Number:
  US 20180348137A1
• Time in Patent Office: 1,161 Days
• CPC Class Codes: G01N 2021/0193 the sample being taken from a stream or flow to the measurement cell
• CPC Class Codes: G01N 2021/0346 Capillary cells; Microcells
• CPC Class Codes: G01N 2021/157 Monitoring by optical means
• CPC Class Codes: G01N 2021/651 Cuvettes therefore
• CPC Class Codes: G01N 21/03 Cuvette constructions
• CPC Class Codes: G01N 21/64 Fluorescence; Phosphorescence
• CPC Class Codes: G01N 21/645 Specially adapted constructive features of fluorimeters
• CPC Class Codes: G01N 21/65 Raman scattering
• CPC Class Codes: G01N 33/5014 for testing toxicity
• CPC Class Codes: G01N 33/5094 for blood cell populations red blood cells G01N33/80
• CPC Class Codes: G21K 1/003 Manipulation of charged particles by using radiation pressure, e.g. optical levitation acceleration of charged particles H05H5/00, H05H7/00, H05H9/00, H05H11/00, H05H13/00

Abstract

The invention relates to a device for analyzing biological objects comprising a Raman spectroscopy system for capturing at least one Raman spectrum. The device comprises an arresting apparatus, which is designed to at least temporarily arrest the biological objects. An electronic computing apparatus is designed to determine a reaction of a biological object arrested by the arresting apparatus to at least one substance in accordance with an evaluation of the at least one Raman spectrum.

Claims

1. A device for analyzing living cells or cell clusters, comprising

a Raman spectroscopy system for acquiring at least one Raman spectrum,

an arresting unit that is configured to at least temporarily arrest a living cell with an optical trap, and

an electronic computing unit that is configured to determine a reaction of the cell arrested by the arresting unit to at least one substance in accordance with an evaluation of the at least one Raman spectrum.

2. The device as claimed in claim 1, wherein the device is configured to repeatedly engage the cell arrested by the arresting unit in order to acquire the at least one Raman spectrum.

3. The device as claimed in claim 1, comprising

an actuator controllable by the electronic computing unit for producing a relative movement between the arresting unit and the Raman spectroscopy system.

4. The device as claimed in claim 3, wherein the electronic computing unit is configured to control the actuator in accordance with distances between at least two cells arrested by the arresting unit.

5. The device as claimed in claim 3, comprising

an image acquisition device coupled to the electronic computing unit that is configured to acquire an image of the cell arrested by the arresting unit,

wherein the electronic computing unit is configured to control the actuator in accordance with the acquired image.

6. The device as claimed in claim 5, wherein the image acquisition device comprises an optical path separate from a lens of the Raman spectroscopy system.

7. The device as claimed in claim 1, wherein the arresting unit comprises holding areas at each of which at least one cell is arrestable.

8. The device as claimed in claim 7, wherein the device is configured to produce a fluid stream flowing over the plurality of holding areas.

9. The device as claimed in claim 8, comprising

a source of electromagnetic radiation that is configured to move the at least one cell from the fluid stream to a holding area and/or from the holding area into the fluid stream.

10. The device as claimed in claim 9, wherein the source of electromagnetic radiation comprises optical tweezers.

11. The device as claimed in claim 7, wherein each of the holding areas is dimensioned such that only exactly one cell is arrestable at each holding area.

12. The device as claimed in claim 7, wherein each of the holding areas is dimensioned such that a plurality of cells are arrestable at each of the holding areas.

13. The device as claimed in claim 1, comprising

a supply unit for supplying the at least one substance to the cell.

14. The device as claimed in claim 13, wherein the electronic computing unit is configured, in accordance with the evaluation of the at least one Raman spectrum, to determine the reaction to a plurality of substances and/or, in accordance with the evaluation of a plurality of Raman spectra, to follow a course of the reaction in a time-dependent manner.

15. The device as claimed in claim 1, wherein the electronic computing unit is configured to detect a drug resistance in accordance with the evaluation of the at least one Raman spectrum.

16. The device as claimed in claim 15, wherein the electronic computing unit is configured, in order to detect the drug resistance, to compare a first Raman spectrum acquired before the supply of the at least one substance with a second Raman spectrum acquired after administration of an active substance.

17. The device as claimed in claim 1, wherein the at least one substance comprises an active substance, a toxin and/or a chemical.

18. The device as claimed in claim 1, wherein the at least one Raman spectrum evaluated by the electronic computing unit is acquired by Raman scattering on the cell.

19. The device as claimed in claim 1, wherein the at least one Raman spectrum evaluated by the electronic computing unit is acquired by Raman scattering on a material different from the cell.

20. The device as claimed in claim 1, wherein the device is configured to determine in parallel the reaction of a plurality of cells to a substance or a plurality of substances, wherein the device is configured to split an excitation beam of the Raman spectroscopy system in order to produce a plurality of electromagnetic beams for holding the plurality of cells and for Raman spectroscopy.

21. The device as claimed in claim 1, wherein the device is configured, in accordance with an evaluation of the at least one Raman spectrum of the cell arrested by the arresting unit, to selectively remove and/or sort said cell.

22. A method for analyzing living cells or cell clusters, comprising:

arresting a living cell with an optical trap,

acquiring at least one Raman spectrum of the arrested cell, and

evaluating the at least one Raman spectrum in order to determine a reaction of the cell to at least one substance.

23. The method as claimed in claim 22, wherein the at least one substance comprises an active substance, a toxin and/or a chemical.

24. The method as claimed in claim 22, which is automatically carried out by a device for analyzing living cells or cell clusters comprising:

a Raman spectroscopy system for acquiring at least one Raman spectrum,

an arresting unit that is configured to at least temporarily arrest the cell with the optical trap, and

an electronic computing unit that is configured to determine a reaction of the cell arrested by the arresting unit to at least one substance in accordance with an evaluation of the at least one Raman spectrum.

25. A method for analyzing living cells or cell clusters, comprising:

arresting a living cell with an optical trap,

acquiring at least one Raman spectrum of the arrested cell, and

evaluating the at least one Raman spectrum in order to determine a reaction of the cell to at least one substance, wherein after evaluation of the at least one Raman spectrum in order to determine a reaction of the cell to at least one substance, the cell is selectively removed and/or sorted.