Microfluidic device and method for detecting rare cells

Patent metadata

Field	Value
Publication number	US-10677708-B2
Application number	US-201816100726-A
Country	US
Kind code	B2
Filing date	Aug 10, 2018
Priority date	Oct 29, 2012
Publication date	Jun 9, 2020
Grant date	Jun 9, 2020

Abstract

A microfluidic device for detecting rare cells in a fluid sample comprises the rare cell and other cells. The microfluidic device comprises an inlet for receiving the fluid sample, a labyrinth channel structure in fluid communication with the inlet, and an outlet in fluid communication with the labyrinth channel structure for collecting the rare cells separated from the other cells in the fluid sample. The labyrinth channel structure comprises at least one channel through which the fluid sample flows. The at least one channel has a plurality of segments and a plurality of corners with each corner defined between adjacent segments. The presence of the plurality of corners induces separation of the rare cells from the other cells in the fluid sample as the rare cells move to a first equilibrium position within the at least one channel when a ratio of inertial lift forces (FZ) and Dean flow (FD) of the fluid sample is from 2 to 10.

First claim

What is claimed is:

1. A microfluidic device for detecting rare cells in a fluid sample comprising the rare cells and other cells, the microfluidic device comprising:
an inlet for receiving the fluid sample;
a labyrinth channel structure in fluid communication with the inlet, wherein the labyrinth channel structure comprises at least one channel having a rectangular cross-section, a width of from 500 to 1000 μm, and a height of from 1 to 150 μm, the at least one channel having a plurality of segments and a plurality of corners with each corner defined between adjacent segments, wherein the plurality of corners are configured to induce a change in fluid flow direction of the fluid sample and a separation of the rare cells from the other cells in the fluid sample; and
an outlet in fluid communication with the at least one channel for collecting the rare cells separated from the other cells in the fluid sample.

2. The microfluidic device of claim 1 , wherein the labyrinth channel structure comprises at least 2 corners.

3. The microfluidic device of claim 1 , wherein the labyrinth channel structure comprises from 40 to 50 corners.

4. The microfluidic device of claim 1 , wherein the labyrinth channel structure is configured to induce in the fluid sample a ratio of inertial lift forces (F z ) and Dean flow (F D ) from 2 to 10 and move the rare cells to a first equilibrium position within the at least one channel.

5. The microfluidic device of claim 4 , wherein the other cells include white blood cells, and the plurality of segments and the plurality of corners of the at least one channel are configured to induce separation of the white blood cells as the white blood cells move to a second equilibrium position within the at least one channel.

6. The microfluidic device of claim 5 , wherein the first equilibrium position defines a first stream comprising rare cells and the second equilibrium position defines a second stream comprising white blood cells, and wherein a spacing between the first and second stream is from 50 to 100 μm.

7. The microfluidic device of claim 1 , wherein the at least one channel has a length of from 1 μm to 1000 μm.

8. The microfluidic device of claim 1 , wherein the labyrinth channel structure is configured to separate at least rare cells and white blood cells, and the outlet comprises a first flow path for the rare cells and a second flow path for the white blood cells.

9. The microfluidic device of claim 1 , wherein each of the plurality of corners induces at least a 90° change in direction of the flow of the fluid sample.

10. A method of detecting rare cells in a fluid sample comprising the rare cells and other cells, the method comprising:
providing a microfluidic device comprising:
an inlet,
a labyrinth channel structure in fluid communication with the inlet, wherein the labyrinth channel structure comprises at least one channel having a rectangular cross-section, a width of from 500 to 1000 μm, and a height of from 1 to 150 μm, the at least one channel having a plurality of segments and a plurality of corners with each corner defined between adjacent segments, and
an outlet in fluid communication with the at least one channel;

introducing the fluid sample into the inlet of the microfluidic device; and
flowing the fluid sample through the labyrinth channel structure of the microfluidic device, wherein flowing the fluid sample through the labyrinth channel structure induces the rare cells to separate from the other cells as the fluid sample flows past the plurality of corners.

11. The method of claim 10 , wherein flowing the fluid sample through the labyrinth channel structure comprises flowing the fluid sample through 40 to 50 corners.

12. The method of claim 10 , wherein introducing the fluid sample into the inlet comprises introducing the fluid sample at a volumetric flow rate of from 0.1 to 30 mL/hr.

13. The method of claim 10 , wherein the other cells comprise white blood cells and flowing the fluid sample through the labyrinth channel structure causes separation of the rare cells into a first stream and the white blood cells into a second stream, and wherein separation between the first and the second stream is from 50 to 100 μm.

14. The method of claim 10 , wherein the other cells comprise white blood cells and the outlet comprises a first flow path for the rare cells and a second flow path for the white blood cells, and wherein the method further comprises collecting the rare cells in the first flow path and collecting the white blood cells in the second flow path.

15. The method of claim 10 , further comprising recovering at least 95% of the rare cells after flowing the fluid sample through the labyrinth channel structure.

16. The method of claim 10 , wherein the rare cells move to a first equilibrium position within the at least one channel and the fluid sample achieves a ratio of inertial lift forces (F z ) and Dean flow (F D ) from 2 to 10 as the fluid sample flows through the labyrinth channel structure.

Assignees

• Univ Michigan Regents

Inventors

• Nagrath Sunitha
• Yoon Hyeun Joong
• Lin Eric
• Wicha Max S
• Baez Lianette Rivera
• Simeone Diane M

Classifications

• B01L2300/0864

  comprising only one inlet and multiple receiving wells, e.g. for separation, splitting · CPC title

• G01N2015/0288

  Sorting the particles · CPC title

• G01N2015/008

  Physics · mapped topic

• B01L3/502761

  specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads or physically stretching molecules · CPC title

• B01L3/502753

  characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation · CPC title