IP Library › Granted Patent US 10,144,009
Granted Patent B2
US 10,144,009 · App. 15/029,627 · Granted Dec 4, 2018

Microfluidics sorter for cell detection and isolation

Inventors: Ali Asgar Bhagat (Singapore, SG); Guofeng Guan (Singapore, SG)
Assignee: CLEARBRIDGE BIOMEDICS PTE LTD
B01L3/502761B01L3/502776G01N15/0255B01L2200/0652B01L2300/0816B01L2300/0819B01L2300/0861G01N2015/0288
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Quick Facts
Patent No.
US 10,144,009
App. No.
15/029,627
Granted
Dec 4, 2018
Kind
B2
Abstract

A microfluidic device is disclosed. The device comprises at least one inlet for receiving circulating tumor cells and other cells in a sample; at least one curvilinear and/or spiral channel through which the sample is caused to undergo partial or complete Dean cycles to isolate the circulating tumor cells from the other cells; and at least one outlet configured to communicate with the channel for providing the isolated circulating tumor cells. The channel is configured to provide a predetermined Force ratio based on a desired threshold cell size of the circulating tumor cells. A corresponding method of manufacturing of the device, and a related diagnostic system are also disclosed.

Claims (67)

1. A microfluidic device comprising:

at least one inlet for receiving circulating tumor cells and other cells in a sample;

at least one curvilinear and/or spiral channel through which the sample is caused to undergo migration along at least a partial Dean vortex to isolate the circulating tumor cells from the other cells;

a flow resistance channel arranged to be coupled to the at least one inlet, the flow resistance channel comprising a series of microchannels to stabilise flow fluctuations;

and at least one outlet in communication with the at least one curvilinear and/or spiral channel for providing the isolated circulating tumor cells, wherein the at least one curvilinear and/or spiral channel is configured to provide a predetermined Force ratio greater than or equal to 2 based on a desired threshold cell size of the circulating tumor cells, the predetermined Force ratio being defined as a ratio of inertial lift force (F L ) to Dean drag force (F D ), and wherein the predetermined Force ratio is further defined according to the equation:

i

F

=

F

L

/

F

D

=

85.11

⁢

⁢

R

C

⁢

a

C

3

h

4

,

where i F is the Force ratio, R c , is the radius of curvature, a c is the cell size, and h is the at least one curvilinear and/or spiral channel height, wherein the threshold cell size is about 15-20 μm.

2. The device of claim 1 , wherein the device is comprised in a biochip in a microfluidic packaging configured as a disposable cartridge.

3. The device of claim 1 , wherein the at least one curvilinear and/or spiral channel height is arranged to be smaller than ten times the threshold cell size.

4. The device of claim 1 , wherein the at least one curvilinear and/or spiral channel has a cross-section having a channel width and a channel height defining an aspect ratio of the at least one curvilinear and/or spiral channel.

5. The device of claim 4 , wherein the at least one curvilinear and/or spiral channel width is arranged to be approximately between 300 μm to 650 μm.

6. The device of claim 5 , wherein the at least one curvilinear and/or spiral channel height is arranged to be approximately between 120 μm to 180 μm.

7. The device of claim 1 , wherein the radius of curvature is configured to be approximately between 5 mm to 20 mm.

8. The device of claim 1 , wherein the at least one outlet includes a first outlet and a second outlet to respectively enable the isolated circulating tumor cells and the other cells to be provided.

9. The device of claim 1 , wherein a total length of the at least one curvilinear and/or spiral channel is arranged to be between 5 cm to 100 cm.

10. The device of claim 9 , wherein the at least one curvilinear and/or spiral channel is an arc and the total length is configured to generate a half dean cycle migration.

11. The device of claim 9 , wherein the at least one curvilinear and/or spiral channel is a spiral and the total length is configured to generate whole number multiples of a dean cycle migration.

12. The device of claim 1 , wherein the at least one inlet includes a first inlet and a second inlet arranged to be coupled to respective damper chambers to regulate a flor rate of the sample the at least one curvilinear and/or spiral channel, wherein the first inlet is for introducing the sample into the at least one curvilinear and/or spiral channel and the second inlet is for introducing a sheath fluid into the at least one curvilinear and/or spiral channel.

13. A diagnostic system configured for detecting circulating tumor cells in a sample comprising: a microfluidic device according to claim 1 configured to isolate the circulating tumor cells from other biological cells in a sample; and a processor configured to generate a diagnostic indication based on the circulating tumor cells isolated by the microfluidic device.

14. A diagnostic system according to claim 13 , wherein the sample is a whole blood sample or a red blood cell depleted blood sample.

15. A method of manufacturing a microfluidic device comprising:

providing at least one inlet for receiving circulating tumor cells and other cells in a sample, and at least one curvilinear and/or spiral channel through which the sample is caused to undergo migration along at least a partial Dean vortex to isolate the circulating tumor cells from the other cells;

providing a flow resistance channel arranged to be coupled to the at least one inlet, the flow resistance channel comprising a series of microchannels to stabilise flow fluctuations;

providing at least one outlet configured for communicating with the at least one curvilinear and/or spiral channel for providing the isolated circulating tumor cells; and

selecting a curvilinear and/or spiral channel height, radius of curvature, and length to provide a predetermined Force ratio greater than or equal to 2 based on a desired threshold cell size of the circulating tumor cells, the predetermined Force ratio being defined as a ratio of inertial lift force (F L ) to Dean drag force (F D ), and wherein the predetermined Force ratio is further defined according to the equation:

i

F

=

F

L

/

F

D

=

85.11

⁢

⁢

R

C

⁢

a

C

3

h

4

,

where i F is the Force ratio, R c , is the radius of curvature, a c is the cell size, and h is the curvilinear and/or spiral channel height, wherein the threshold cell size is about 15-20 μm.

Assignments (2)
CORRECTION OF ADDRESS Recorded Nov 11, 2019
From: CLEARBRIDGE BIOMEDICS PTE. LTD.
To: BIOLIDICS LIMITED
Reel/Frame 050979/0611 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 15, 2016
From: BHAGAT, ALI ASGAR; GUAN, GUOFENG
To: CLEARBRIDGE BIOMEDICS PTE LTD
Reel/Frame 038293/0605 →
Continuity (1)
Related Publication 20160303565A1 · Oct 20, 2016
Cited By (4)
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