Analysis and sorting of objects in flow

Patent metadata

Field	Value
Publication number	US-9734577-B2
Application number	US-201615352311-A
Country	US
Kind code	B2
Filing date	Nov 15, 2016
Priority date	Dec 7, 2011
Publication date	Aug 15, 2017
Grant date	Aug 15, 2017

Abstract

A device and method for sorting objects immersed in a flowing medium are disclosed. An example device comprises a holographic imaging unit comprising one or more holographic imaging elements, a fluid handling unit comprising one or more microfluidic channels configured to conduct flowing medium along a corresponding holographic imaging element and at least one microfluidic switch arranged downstream of an imaging region in the microfluidic channel configured to direct objects in the flowing medium into a one of a plurality of outlets. The example device also comprises a processor configured to determine real-time characterizations of holographic diffraction images obtained for the moving objects. The processing unit is further configured to control the at least one microfluidic switch in response to the real-time characterizations.

First claim

The invention claimed is:

1. A device configured to sort objects immersed in a flowing medium, the device comprising:
a holographic imaging unit including a CMOS or CCD image sensor partitioned into a plurality of holographic imaging elements configured to provide a plurality of holographic diffraction images, wherein each imaging element comprises an array of imaging pixels;
a fluid handling unit including an imaging region and a switch arranged downstream of the imaging region, wherein the fluidic handling unit is configured to conduct the flowing medium along a corresponding holographic imaging element in the imaging region, and wherein the switch is configured to direct one or more objects in the flowing medium to one or more outlets of a plurality of outlets; and
a processor configured to:
based on at least one holographic diffraction image of the plurality of holographic diffraction images, determine a real-time characterization of the one or more objects that pass through the imaging region; and
in response to the real-time characterization, control the switch to direct the one or more objects in the flowing medium to the one or more outlets.

2. The device according to claim 1 , wherein the image sensor is configured for parallel readout of the plurality of imaging elements thereby providing the plurality of holographic diffraction images simultaneously and independently from each other.

3. The device according to claim 1 , further comprising a detector unit configured to generate a trigger signal that is representative of a detected presence of the one or more objects in the flowing medium upstream of the imaging region.

4. The device according to claim 3 , wherein the detector unit comprises a photodetector configured to receive light modulated by moving objects, or at least one electrode configured to detect a change in an electrical signal caused by moving objects.

5. The device according to claim 3 , wherein the processor is configured to determine the real-time characterization of the one or more objects based on the trigger signal and on the at least one holographic diffraction image.

6. The device according to claim 3 , wherein the holographic imaging elements are configured to provide the holographic diffraction images in response to the trigger signal.

7. The device according to claim 3 , wherein the detector unit is upstream from the imaging region.

8. The device according to claim 1 , wherein the holographic imaging elements are configured to:
evaluate a detection criterion related to detecting the presence of the one or more objects in the flowing medium, and
responsive to the detection criterion being satisfied, transmit the holographic diffraction images to the processor.

9. The device according to claim 1 , further comprising at least one flow monitoring device configured to provide flow information relating to at least one of a velocity or an acceleration of the one or more objects in the flowing medium, and wherein the processor is configured to, responsive to the flow information and the real-time characterization, control the switch to direct the one or more objects in the flowing medium to the one or more outlets.

10. The device according to claim 9 , wherein the processor is configured to:
determine, responsive to the flow information, a predicted time of arrival of the one or more objects in at least one of the imaging region or at the switch; and
control, responsive to the predicted time of arrival, at least one of the one or more holographic imaging elements to provide the holographic diffraction images, or the switch to direct the one or more objects in the flowing medium to the one or more outlets.

11. The device according to claim 1 , wherein the fluid handling unit further comprises a focusing unit configured to concentrate the one or more objects in a central region of the flowing medium through the imaging region, and wherein the focusing unit includes a channel dimensioned to twice the size of the objects in the flowing medium.

12. The device according to claim 1 , wherein the fluid handling unit includes a plurality of microfluidic channels configured to conduct the flowing medium along the imaging region and to the switch.

13. The device according to claim 1 , wherein the imaging region is arranged at an angle with respect to a grid alignment of a respective image sensor, and wherein the processor is further configured to receive a plurality of holographic diffraction images from the holographic imaging unit, and to construct a super-resolution holographic diffraction image from the plurality of holographic diffraction images obtained for the one or more objects in the flowing medium.

14. A method comprising:
introducing a flow of a fluid into one or more channels, wherein the one or more channels include an imaging region;
recording, using a CMOS or CCD image sensor, a plurality of holographic diffraction images of one or more objects in the fluid as the one or more objects pass through the imaging region, wherein the image sensor is partitioned into a plurality of holographic imaging elements, and each imaging element comprising an array of imaging pixels;
characterizing the one or more objects in the plurality of holographic diffraction images wherein a characterization of each object accounts for at least one predetermined object type signature; and
based on the characterization of each object, directing the one or more objects into one of a plurality of outlets.

15. The method according to claim 14 , wherein the recording of the plurality of holographic diffraction images further comprises parallel readout of the imaging elements thereby providing the plurality of holographic diffraction images simultaneously and independently from each other.

16. The method according to claim 14 , further comprising generating a synchronization signal that is representative of a detected presence of one or more objects in the fluid upstream of the imaging region, wherein characterizing the one or more objects is performed responsive to the synchronization signal.

17. The method according to claim 16 , wherein recording the plurality of holographic diffraction images is performed in response to the synchronization signal.

18. The method according to claim 14 , further comprising monitoring the flowing fluid to provide flow information relating to at least one of a velocity or an acceleration of the one or more objects in the fluid, wherein directing the one or more objects into one of a plurality of outlets is performed responsive to the flow information and the characterization of the one or more objects.

19. The method according to claim 18 , further comprising:
determining, responsive to the flow information, a predicted time of arrival of the one or more objects in at least one of the imaging region or at a switching region, wherein objects are directed into one of a plurality of outlets from the switching region; and
controlling, responsive to the predicted time of arrival, at least one of the recording of the plurality of holographic diffraction images, or the directing of the one or more objects into one of a plurality of objects.

20. The method according to claim 14 , wherein the one or more channels includes a focusing unit configured to concentrate the one or more objects in a central region of the flowing fluid through the imaging region, wherein the focusing unit includes a channel dimensioned to twice the size of the objects in the fluid.

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

• G01N2015/1445

  Three-dimensional imaging, imaging in different image planes, e.g. under different angles or at different depths, e.g. by a relative motion of sample and detector, for instance by tomography · CPC title

• G06T7/20

  Analysis of motion (motion estimation for coding, decoding, compressing or decompressing digital video signals H04N19/43, H04N19/51) · CPC title