Analysis and sorting of objects in flow

Patent metadata

Field	Value
Publication number	US-9495742-B2
Application number	US-201214363373-A
Country	US
Kind code	B2
Filing date	Dec 7, 2012
Priority date	Dec 7, 2011
Publication date	Nov 15, 2016
Grant date	Nov 15, 2016

Abstract

A device and method for sorting objects immersed in a flowing medium are described. An example device comprises a holographic imaging unit comprising a plurality of holographic imaging elements, a fluid handling unit comprising a plurality of microfluidic channels for conducting flowing medium along a corresponding holographic imaging element and a microfluidic switch arranged downstream of an imaging region in the microfluidic channel for directing each object in the flowing medium into a one of a plurality of outlets. The example device also comprises a processing unit configured to determine real-time characterizations of holographic diffraction images obtained for each of the moving objects, with each real-time characterization accounting for at least one predetermined object-type signature. The processing unit is further adapted for controlling the microfluidic switches in response to the real-time characterizations.

First claim

The invention claimed is:

1. A device configured for sorting objects immersed in a flowing medium, the device comprising:
a holographic imaging unit comprising one or more holographic imaging elements configured to provide a plurality of holographic diffraction images;
a fluid handling unit comprising one or more microfluidic channels, wherein each microfluidic channel of the one or more microfluidic channels comprises (i) an imaging region for conducting the flowing medium along a corresponding holographic imaging element for imaging a moving object immersed in the flowing medium, and (ii) a microfluidic switch arranged downstream of the imaging region for directing the object in the flowing medium into an outlet of a plurality of outlets;
synchronization means for generating a synchronization signal that is at least one of (i) representative of a detected presence of a first object immersed in the flowing medium upstream of a first imaging region, or (ii) representative of a detected presence of the first object upstream of a first microfluidic switch, and wherein the synchronization means is incorporated in at least one of a first holographic imaging element or in a wall of a first microfluidic channel; and
a processor configured to: (i) receive a first holographic diffraction image from the holographic imaging unit; (ii) in response to the synchronization signal and based on at least the first holographic diffraction image, determine a real-time characterization of the first object that passes through the first imaging region of the first microfluidic channel; and (iii) in response to the real-time characterization, control the first microfluidic switch downstream of the first imaging region,
wherein the real-time characterization accounts for at least one predetermined object-type signature, wherein the first microfluidic channel is included in the one or more microfluidic channels, and wherein the first microfluidic channel includes the first imaging region, the first holographic imaging element, and the first microfluidic switch.

2. The device according claim 1 , wherein each of the one or more holographic imaging elements is configured to receive and to process the synchronization signal from a corresponding synchronization means.

3. The device according to claim 1 , wherein the synchronization means comprises a photodetector configured to receive light modulated by moving objects.

4. The device according to claim 1 , wherein the synchronization means comprises at least one electrode configured to detect a change in an electrical signal caused by moving objects.

5. The device according to claim 1 , wherein each microfluidic channel further comprise a meandering segment arranged between the imaging region and the microfluidic switch, wherein the meandering segment slows the transit of moving objects from the imaging region to the microfluidic switch.

6. The device according to claim 1 , wherein the one or more microfluidic channels includes a plurality of microfluidic channels arranged in a cascade such that at least one outlet of the first microfluidic channel feeds the flowing medium into a second microfluidic channel, wherein the first microfluidic channel and the second microfluidic channel are included in the plurality of microfluidic channels.

7. The device according to claim 1 , wherein the holographic imaging unit comprises an image sensor, and wherein the image sensor comprises at least one of a CMOS image sensor or a CCD image sensor.

8. The device according to claim 7 , wherein, for each microfluidic channel, the imaging region is arranged at an angle with respect to a grid alignment of the image sensor, and wherein the processor is further configured to: (iv) receive a plurality of holographic diffraction images from the holographic imaging unit; and (v) construct a super-resolution holographic diffraction image from the plurality of holographic diffraction images obtained for the first object.

9. The device according to claim 1 , further comprising one or more fluorescence imaging elements configured to provide a plurality of fluorescence images, wherein, for each microfluidic channel, the imaging region is further configured to direct the flowing medium along a corresponding fluorescence imaging element included in the one or more fluorescence imaging elements.

10. The device according to claim 9 , wherein each of the one or more fluorescence imaging elements comprises a multi-spectral filter assembly.

11. The device according to claim 9 , wherein the processor is configured to receive a first fluorescence image from a first fluorescence imaging element that is included in the one or more fluorescence imaging elements, wherein the real-time characterization is further based on the first fluorescence image.

12. The device according to claim 1 , wherein each microfluidic channel further comprises a focusing unit for concentrating the moving objects in a central region of the flowing medium through the imaging region.

13. The device according to claim 1 , wherein the fluid handling unit further comprises an inlet for distributing the flowing medium over at least two of a plurality of microfluidic channels.

14. The device according to claim 1 , wherein the holographic imaging unit comprises at least one at least partially-coherent pulsed light source configured to illuminate the flowing medium.

15. The device according to claim 14 , wherein the at least one at least partially-coherent pulsed light source comprises a plurality of light sources configured to illuminate the flowing medium at different angles.

16. The device according to claim 15 , wherein the holographic imaging unit further comprises an image sensor and at least one polarizer, wherein the at least one polarizer is optically coupled to the at least one at least partially-coherent pulsed light source and to the image sensor, and wherein the at least one polarizer is configured to filter one or more polarization-sensitive features.

17. The device according to claim 15 , wherein the at least one at least partially-coherent light source emits light at one or more wavelengths.

18. The device according to claim 15 , wherein the at least one at least partially-coherent light source comprises a pinhole aperture arranged on each microfluidic channel in the one or more microfluidic channels.

19. The device according to claim 1 , wherein, for each microfluidic channel, the microfluidic switch comprises at least one of a thermally-driven flow detection means or a piezoelectric-driven flow deflection means.

20. The device according to claim 1 , wherein, for each microfluidic channel, the microfluidic switch comprises at least one micro-heater configured to generate vapor bubbles that displace the moving objects in the flowing medium.

21. The device according to claim 1 , wherein, for each microfluidic channel, the microfluidic switch comprises a fluidic side chamber and an actuator configured to adjust a volume of the fluidic side chamber in order to change a trajectory of moving objects in the flowing medium, wherein the actuator is at least one of a piezoelectric actuator or a thermal actuator.

22. The device according to claim 1 , wherein, for each microfluidic channel, the microfluidic switch comprises a fluidic side chamber and an externally actuated moveable membrane configured to adjust a volume of the fluidic side chamber in order to change a trajectory of moving objects in the flowing medium.

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Assignees

• Imec
• Univ Leuven Kath

Inventors

• Lagae Liesbet
• Peumans Peter
• Verstreken Kris
• Vercruysse Dries
• Liu Chengxun

Classifications

• G01N15/1436 Primary

  the optical arrangement forming an integrated apparatus with the sample container, e.g. a flow cell · CPC title

• G06T7/0012 Primary

  Biomedical image inspection · CPC title

• G06F18/24

  Classification techniques · CPC title

• G03H1/22

  Processes or apparatus for obtaining an optical image from holograms (G03H1/26 - G03H1/34 take precedence) · CPC title

• G01N15/147

  the analysis being performed on a sample stream · CPC title