Particle separation and concentration using spiral inertial filtration

Patent metadata

Field	Value
Publication number	US-9804068-B2
Application number	US-201314042043-A
Country	US
Kind code	B2
Filing date	Sep 30, 2013
Priority date	Sep 28, 2012
Publication date	Oct 31, 2017
Grant date	Oct 31, 2017

Abstract

A spiral inertial filtration device is capable of high-throughput (1 mL/min), high-purity particle separation while concentrating recovered target particles by more than an order of magnitude. Large fractions of sample fluid are removed from a microchannel without disruption of concentrated particle streams by taking advantage of particle focusing in inertial spiral microfluidics, which is achieved by balancing inertial lift forces and Dean drag forces. To enable the calculation of channel geometries in the device for specific concentration factors, an equivalent circuit model was developed and experimentally validated. Large particle concentration factors were achieved by maintaining either average fluid velocity or Dean number throughout the entire length of the channel during the incremental removal of sample fluid. Also provided is the ability to simultaneously separate more than one particle from the same sample.

First claim

The invention claimed is:

1. A fluid processing apparatus configured for separating particles from a fluid flowing through the apparatus, the apparatus comprising:
a fluid inlet configured to receive a fluid containing particles;
a main fluid channel extending from said fluid inlet and arranged in a spiral configuration and configured to cause differential migration of particles within the fluid flowing through said main fluid channel into unique equilibrium positions within said main channel according to a size of the particle thereby forming one or more particle streams and a particle-free region within the fluid flowing through said main channel;
one or more outlets in fluid communication with said main fluid channel and configured to receive the particles from the one or more particle streams flowing from said main fluid channel; and
one or more secondary channels extending from said main fluid channel along a length of said main fluid channel between the fluid inlet and the one or more outlets and configured to draw at least a portion of the fluid from the particle-free region within said main channel to increase the concentration of particles within the remaining fluid flowing through said main channel, wherein the main channel has a non-uniform geometry, wherein the geometry of the main channel is changed following a secondary channel to compensate for fluid removal via the secondary channel.

2. The fluid processing apparatus of claim 1 , wherein the one or more particles sizes are in a range of 4.8 μm to 15 μm.

3. The fluid processing apparatus of claim 1 , wherein the secondary channels are configured to draw a portion of the fluid of the particle-free region from said main channel to reduce the volume of fluid flowing through said main channel by about 10-95%.

4. The fluid processing apparatus of claim 1 , wherein the particles are selected from the group consisting of DNA molecules, viruses, bacteria, fungi, cancer cells, white blood cells, and neutrophils.

5. The fluid processing apparatus of claim 1 , wherein the fluid flowing through the apparatus comprises a sample and the particles comprise more than one component of interest within the sample, and wherein
the fluid inlet is configured to receive the sample;
the main fluid channel is configured so that the components of interest are focused into more than one component stream according to the size of the components, thereby forming a component-free region within the fluid flowing through said main channel;
the apparatus includes more than one outlet in fluid communication with said main fluid channel and configured to receive the components of interest from the component streams flowing from said main fluid channel to filter each of the components of interest from the sample; and
the one or more secondary channels are configured to draw at least a portion of the fluid from the component-free region within said main channel to increase the concentration of components of interest within the remaining fluid flowing through said main channel.

6. The fluid processing apparatus of claim 1 , wherein said fluid inlet is located at an inner end portion of the spiral configuration of said main channel, the one or more outlets are located at an outer end portion of the spiral configuration of the main channel, and said one or more secondary channels extend radially outwardly from an outer loop of the spiral configuration of said main channel.

7. The fluid processing apparatus of claim 1 , wherein said main channel has a non-uniform width varying along the length of said main channel.

8. The fluid processing apparatus of claim 7 , comprising at least two secondary channels, and wherein the width of said main channel is substantially constant between each two neighboring secondary channels.

9. The fluid processing apparatus of claim 1 , wherein the geometry of said main channel is changed following a secondary channel to compensate for fluid removal via the secondary channel.

10. The fluid processing apparatus of claim 9 , wherein the geometry of said main channel is changed following a secondary channel to maintain a constant or substantially constant flow velocity within said main channel before and after the secondary channel.

11. The fluid processing apparatus of claim 10 , wherein the geometry of said main channel is changed by changing the width of the main channel, and the new width w m,j , of the main channel following a j th secondary channel is determined by the formula:
w m,j−1 =x m,j−1 w m,j ,

wherein x m,j−1 is the fraction of fluid remaining in the main channel after fluid removal through the jth secondary channel, and w m,j is the width of the previous section of said main channel.

12. The fluid processing apparatus of claim 9 , wherein the geometry of said main channel is changed following a secondary channel to maintain a constant or substantially constant Dean number, De, within said main channel before and after the secondary channel, wherein the Dean number, De, is given by the formula:

De
=

ρ
⁢

⁢

U
f

⁢

D
h

μ

⁢

D
h

2
⁢
R

wherein ρ is the density of the fluid, U f is average fluid velocity, μ is fluid dynamic viscosity, R is the radius of curvature of said main channel, and D h is a hydraulic diameter, and wherein the hydraulic diameter, D h , is determined from:

D
h

=

2
⁢
wh

w
+
h

,

wherein w is the width of said main channel and h is the height of said main channel.

13. The fluid processing apparatus of claim 9 , wherein the geometry of said main channel is changed by changing the width of the main channel.

14. The fluid processing apparatus of claim 13 , wherein a downstream corner of a junction between said main channel and said secondary channel is filleted to allow for a gradual change in the width of said main channel.

15. The fluid processing apparatus of claim 1 , comprising between one and five outlets.

16. The fluid processing apparatus of claim 1 , comprising between one and six secondary channels.

17. The fluid processing apparatus of claim 1 , wherein each secondary channel extends from an outer edge of an outer-most ring of the spiral configuration of said main channel.

18. The fluid proce

Assignees

• Canon Us Life Sciences Inc
• Univ Maryland

Inventors

• Burke Jeffrey M
• White Ian M

Classifications

• B01D21/265

  by using a vortex inducer or vortex guide, e.g. coil (B01D21/0054 takes precedence) · CPC title

• G01N1/34 Primary

  Purifying; Cleaning {(processes or apparatus for extracting or separating nucleic acids from biological samples C12N15/1003)} · CPC title

• B01L2200/0636

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

• B01L3/502753

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

• B01D21/0087

  Settling tanks provided with means for ensuring a special flow pattern, e.g. even inflow or outflow (B01D21/2411 takes precedence) · CPC title