Microfluidics sorter for cell detection and isolation

Patent metadata

Field	Value
Publication number	US-9458489-B2
Application number	US-201113582263-A
Country	US
Kind code	B2
Filing date	Mar 4, 2011
Priority date	Mar 4, 2010
Publication date	Oct 4, 2016
Grant date	Oct 4, 2016

Abstract

A method of detecting one or more diseased blood cells in a blood sample includes introducing a blood sample into at least one inlet of a microfluidic device comprising one or more linear channels wherein each channel has a length and a cross-section of a height and a width defining an aspect ratio adapted to isolate diseased blood cells along at least one portion of the cross-section of the channel based on reduced deformability of diseased blood cells as compared to non-diseased blood cells, wherein diseased blood cells flow along a first portion of the channel to a first outlet and non-diseased blood cells flow along a second portion of the channel to a second outlet. The one or more channels can be adapted to isolate cells along portions of the cross-section of the channel based on cell size. In some embodiments, the one or more channels can be spiral channels.

First claim

What is claimed is:

1. A method of isolating one or more circulating tumor cells comprising:
introducing a sample into a microfluidic device, the sample comprising a whole blood sample or a maternal whole blood sample, wherein the whole blood sample or the maternal whole blood sample comprises one or more circulating tumor cells to be isolated and smaller blood cells, the microfluidic device comprising a channel having a length, L c , and a cross-section of a height in the range of between about 10 μm and about 200 μm and a width in the range of between about 100 μm and about 500 μm defining an aspect ratio adapted to isolate circulating cells along portions of the cross-section of the channel based on cell size,
the channel comprising one or more spiral channels and having a hydraulic diameter, h, such that a cell diameter, a c , of the circulating tumor cells to be isolated satisfies the ratio: a c /h˜0.1, whereas the smaller blood cells have a smaller cell diameter than a c such that the ratio a c /h˜0.1 is not satisfied for those cells,
introducing a sheath fluid into the microfluidic device,
flowing the sample through the channel at an average flow velocity, U f , that causes the smaller blood cells to have undergone a transverse one-half Dean cycle migration across the channel at an outlet end of the channel such that the relation

L
C

=

U
f

U
Dean

⨯

L
DC

⨯

1
2

is satisfied, where L c is the length of the channel, U f is the average flow velocity, U Dean is Dean velocity and L DC is a length for a complete Dean cycle migration around the channel, and
detecting and isolating the one or more circulating tumor cells from the sample,
wherein the introducing the sample and the introducing the sheath fluid comprises simultaneously introducing the sample and the sheath fluid into the microfluidic device via a radially innermost inlet and a radially outermost inlet, respectively, to confine the sample to a radially innermost portion of the channel at the inlet, and
wherein the detecting and isolating comprises the one or more circulating tumor cells flowing along a radially innermost portion of the channel to a first outlet and the smaller blood cells in the sample flowing along a radially outermost portion of the channel to a second outlet.

2. The method of claim 1 , further comprising collecting circulating tumor cells from the first outlet.

3. The method of claim 2 , further comprising analyzing the circulating tumor cells.

4. The method of claim 3 , wherein analyzing the circulating tumor cells includes assessing effectiveness of a therapeutic treatment.

5. The method of claim 1 , wherein the width of the channel at the end distal from the inlet is on the order of the cells to be isolated.

6. The method of claim 1 , wherein the microfluidic device further includes at least one cell focusing region having a cross section adapted to cause all cells to migrate to and move along the longer channel dimension.

7. The method of claim 1 , wherein the flowrate within the microfluidic device ranges from a Reynolds number of 10 to 150.

Assignees

• Lim Chwee Teck
• Han Jongyoon
• Hou Han Wei
• Bhagat Ali Asgar
• Van Vliet Krystyn J
• Lee Wong Cheng
• Massachusetts Inst Technology
• Nat Univ Singapore

Inventors

• Lim Chwee Teck
• Han Jongyoon
• Hou Han Wei
• Bhagat Ali Asgar
• Van Vliet Krystyn J
• Lee Wong Cheng

Classifications

• 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

• G01N2015/1415

  Control of particle position · CPC title

• B01L2400/086

  using baffles or other fixed flow obstructions · CPC title

• B01L2200/0636

  Focussing flows, e.g. to laminate flows · CPC title

• B01L2400/0457

  passive flow or gravitation · CPC title