Measuring device and method for determining mass and/or mechanical properties of a biological system

Patent metadata

Field	Value
Publication number	US-10564182-B2
Application number	US-201515119432-A
Country	US
Kind code	B2
Filing date	Feb 17, 2015
Priority date	Feb 17, 2014
Publication date	Feb 18, 2020
Grant date	Feb 18, 2020

Abstract

The invention relates to a measuring device and a method for determining mass and/or mechanical properties of a biological system.

First claim

The invention claimed is:

1. A measuring device for determining mass and/or mechanical properties of a biological system comprising a micro-cantilever and an intensity modulated light source exciting the micro-cantilever, wherein the micro-cantilever is functionalized to adhere to the biological system, and wherein the micro-cantilever is at least partially transparent for a wavelength of the visual spectrum.

2. The measuring device according to claim 1 , wherein the micro-cantilever is fully immersed in a buffer solution.

3. The measuring device according to claim 1 , wherein the micro-cantilever is transparent for a wavelength of the visual spectrum.

4. The measuring device according to claim 1 , wherein the measuring device comprises an optical microscope.

5. The measuring device according to claim 4 , wherein said optical microscope is at least one selected from the group consisting of a fluorescence microscope, a confocal microscope, a fluorescence energy transfer (FRET) microscope, a DIC and a phase contrast microscope, all of those in particular construed as an inverted microscope.

6. The measuring device according to claim 1 , wherein the micro-cantilever has a length in the range of 10 μm to 1000 μm and/or a resonance frequency in a range of 1 Hz to 10 MHz when immersed in water and/or an oscillation amplitude in the range of 0,01 nm to 300 nm and/or the light source is a laser with a wavelength in the range of 350 nm to 750 nm.

7. The measuring device according to claim 6 , wherein the micro-cantilever has a length in the range in the size of 10 μm to 100 μm and/or a resonance frequency in the range of 20 kHz to 1200 kHz when immersed in water and/or an oscillation amplitude smaller than 30 nm and/or the light source is a laser with a wavelength in the range of in a range of 350 nm to 550 nm.

8. The measuring device according to claim 7 , wherein the micro-cantilever has a resonance frequency in the range of 20 kHz to 400 kHz when immersed in water and/or the light source is a laser with a wavelength in the range of in a range of 350 nm to 450 nm.

9. The measuring device according to claim 1 , wherein the light source is focused on a spot and the spot of the light source and the site where the sample is attached are on opposite faces of the cantilever.

10. The measuring device according to claim 1 , wherein the light source spot is focused on the base of the cantilever.

11. The measuring device according to claim 1 , wherein the light source spot is smaller than 100 μm in diameter.

12. The measuring device according to claim 11 , wherein the light source spot is 30 μm in diameter.

13. The measuring device according to claim 11 , wherein the light source spot is smaller than 10 μm in diameter.

14. A method for determining mass and/or mechanical properties of a biological system, said method comprising the steps of:
a. determining a spring constant of a cantilever, in particular a cantilever of a measuring device according to claim 1 ;
b. exciting the cantilever with a light source at a certain frequency;
c. measuring resonance frequency and/or amplitude and phase of the movement of the cantilever before attaching a biological system;
d. approaching the cantilever to the chosen biological system within the sample;
e. attaching the biological system to the cantilever;
f. measuring resonance frequency and/or amplitude and phase of the movement of the cantilever to compare with the resonance frequency obtained in step c); and
g. computing mass and/or mechanical properties of the biological system.

15. The method according to claim 14 , performing the calibration in step a) by:
a′ exciting the cantilever with a laser with a certain frequency; and
b′ measuring the resonance frequency of the cantilever.

16. The method according to claim 14 , comprising the additional steps performed before step a) of:
a″ choosing a biological system; and
b″ adapting the cantilever dimensions to the chosen biological system.

17. The method according to claim 16 , wherein a feedback loop is used.

18. The method according to claim 17 , comprising the step of using the phase of the cantilever as a control variable and the frequency of the signal used to modulate the laser intensity as a manipulated variable.

19. The method according to claim 17 , comprising the step of using an oscillation amplitude of the cantilever as the control variable and an amplitude of the signal used to modulate the laser intensity as a manipulated variable.

20. The method according to claim 17 , wherein fundamental and/or higher flexural modes of the cantilever are used.

Assignees

• Univ Basel
• Eth Zuerich

Inventors

• Martinez-Martin David
• Mueller Daniel J
• Martin Sascha
• Gerber Christoph
• Bircher Benjamin

Classifications

• G01Q30/025 Primary

  Optical microscopes coupled with SPM · CPC title

• G01G9/00

  Methods of, or apparatus for, the determination of weight, not provided for in groups G01G1/00 - G01G7/00 · CPC title

• G01N21/65

  Raman scattering · CPC title

• G01N2021/6441

  with two or more labels · CPC title

• G02B21/0088

  Inverse microscopes · CPC title