U.S. patent application number 11/122139 was filed with the patent office on 2005-09-15 for microfluidic device for concentrating particles in a concentrating solution.
This patent application is currently assigned to Micronics, Inc.. Invention is credited to Bardell, Ronald L., Weigl, Bernhard H..
Application Number | 20050201903 11/122139 |
Document ID | / |
Family ID | 23076003 |
Filed Date | 2005-09-15 |
United States Patent
Application |
20050201903 |
Kind Code |
A1 |
Weigl, Bernhard H. ; et
al. |
September 15, 2005 |
Microfluidic device for concentrating particles in a concentrating
solution
Abstract
A microfluidic device for concentrating particles in a
concentrating solution. A sample and a concentrating fluid flow
laminarly with a microfluidic channel wherein the concentrating
fluid is formulated such that it extracts fluid from the sample and
thus concentrates the particles in the sample.
Inventors: |
Weigl, Bernhard H.;
(Seattle, WA) ; Bardell, Ronald L.; (St. Louis
Park, MN) |
Correspondence
Address: |
SEED INTELLECTUAL PROPERTY LAW GROUP PLLC
701 FIFTH AVE
SUITE 6300
SEATTLE
WA
98104-7092
US
|
Assignee: |
Micronics, Inc.
Redmond
WA
|
Family ID: |
23076003 |
Appl. No.: |
11/122139 |
Filed: |
May 4, 2005 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
11122139 |
May 4, 2005 |
|
|
|
10114765 |
Apr 3, 2002 |
|
|
|
60281114 |
Apr 3, 2001 |
|
|
|
Current U.S.
Class: |
422/400 |
Current CPC
Class: |
B01L 3/5027 20130101;
B01L 3/502746 20130101; G01N 2015/1411 20130101; F16K 99/0059
20130101; B01L 3/502738 20130101; B01L 3/502761 20130101; G01N
2001/4016 20130101; F16K 99/0025 20130101; B01L 2300/0861 20130101;
F16K 2099/0084 20130101; B01L 2200/027 20130101; A61M 2206/11
20130101; A61M 1/14 20130101; B01L 2400/0457 20130101; B01L
2200/028 20130101; F16K 7/17 20130101; Y10T 436/25375 20150115;
B01L 2300/0883 20130101; B01D 21/283 20130101; G01N 2001/4094
20130101; B01L 2300/0829 20130101; G01N 15/1456 20130101; F16K
99/0001 20130101; G01N 2015/1413 20130101; Y10T 436/2575 20150115;
B01L 2200/0668 20130101; B01L 2400/0406 20130101; B01L 2400/0487
20130101; B01L 3/502707 20130101; B01L 2400/084 20130101; F16K
99/0015 20130101; F16K 2099/008 20130101; G01N 15/05 20130101; G01N
2015/1486 20130101; B01D 21/0012 20130101; B01L 2400/0436 20130101;
B01L 2200/0636 20130101; G01N 2015/0288 20130101; B01L 3/502753
20130101; B01L 2200/0647 20130101; G01N 2015/144 20130101; G01N
2035/00247 20130101; B01L 3/502776 20130101; B01L 3/50273 20130101;
B01L 2300/0874 20130101; G01N 15/0255 20130101; G01N 2001/4061
20130101 |
Class at
Publication: |
422/100 |
International
Class: |
B01L 003/00 |
Claims
1-7. (canceled)
8. A method for increasing the concentration of particles in a
sample fluid, the sample fluid comprising the particles and solvent
molecules, the method comprising: providing a microfluidic device
comprising a first inlet channel, a second inlet channel, and a
main diffusion channel connected to the first and second inlet
channels; flowing the sample fluid through the first inlet channel
into the main diffusion channel; flowing a concentrating fluid
through the second inlet channel into the main diffusion channel;
and flowing the sample fluid and concentrating fluid in laminar
flow through the main diffusion channel, such that a fluid
interface is formed between the sample fluid and the concentrating
fluid, and solvent molecules diffuse across the fluid interface
from the sample fluid into the concentrating fluid thereby
increasing the concentration of the particles in the sample
fluid.
9. The method of claim 8 wherein the concentrating fluid comprises
ionic particles.
10. The method of claim 9 wherein the ionic particles have a larger
size than the solvent molecules.
11. The method of claim 8 wherein the concentrating solution
comprises an immiscible solution with a chemical affinity for the
solvent molecules.
12. The method of claim 8 wherein the average flow speeds of the
sample fluid and the concentrating fluid are different.
13. The method of claim 8 wherein the sample fluid and the
concentrating fluid are immiscible.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims benefit from U.S. Provisional Patent
Application Ser. No. 60/281,114, filed Apr. 3, 2001, which
application is incorporated herein by reference.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] This invention relates generally to microfluidic devices for
performing analytic testing, and, in particular, to a device in
which the concentration of a particle in a solvent is increased by
flowing it in contact with a solution that extracts solvent.
[0004] 2. Description of the Related Art
[0005] Microfluidic devices have recently become popular for
performing analytic testing. Using tools developed by the
semiconductor industry to miniaturize electronics, it has become
possible to fabricate intricate fluid systems which can be
inexpensively means produced. Systems have been developed to
perform a variety of analytical techniques for the acquisition of
information for the medical field.
[0006] Microfluidic devices may be constructed in a multi-layer
laminated structure where each layer has channels and structures
fabricated from a laminate material to form microscale voids or
channels where fluids flow. A microscale channel is generally
defined as a fluid passage which has at least one internal
cross-sectional dimension that is less than 500 .mu.m and typically
between about 0.1 .mu.m and about 500 .mu.m. The control and
pumping of fluids through these channels is affected by either
external pressurized fluid forced into the laminate, or by
structures located within the laminate.
[0007] U.S. Pat. No. 5,716,852 teaches a method for analyzing the
presence and concentration of small particles in a flow cell using
diffusion principles. This patent, the disclosure of which is
incorporated herein by reference, discloses a channel cell system
for detecting the presence of analyte particles in a sample stream
using a laminar flow channel having at least two inlet means which
provide an indicator stream and a sample stream, where the laminar
flow channel has a depth sufficiently small to allow laminar flow
of the streams and length sufficient to allow diffusion of
particles of the analyte into the indicator stream to form a
detection area, and having an outlet out of the channel to form a
single mixed stream. This device, which is known at a T-Sensor, may
contain an external detecting means for detecting changes in the
indicator stream. This detecting means may be provided by any means
known in the art, including optical means such as optical
spectroscopy, or absorption spectroscopy of fluorescence.
[0008] U.S. Pat. No. 5,932,100, which patent is also incorporated
herein by reference, teaches another method for analyzing particles
within microfluidic channels using diffusion principles. A mixture
of particles suspended in a sample stream enters an extraction
channel from one upper arm of a structure, which comprises
microchannels in the shape of an "H". An extraction stream (a
dilution stream) enters from the lower arm on the same side of the
extraction channel and due to the size of the microfluidic
extraction channel, the flow is laminar and the streams do not mix.
The sample stream exits as a by-product stream at the upper arm at
the end of the extraction channel, while the extraction stream
exits as a product stream at the lower arm. While the streams are
in parallel laminar flow is in the extraction channel, particles
having a greater diffusion coefficient (smaller particles such as
albumin, sugars, and small ions) have time to diffuse into the
extraction stream, while the larger particles (blood cells) remain
in the sample stream. Particles in the exiting extraction stream
(now called the product stream) may be analyzed without
interference from the larger particles. This microfluidic
structure, commonly known as an "H-Filter," can be used for
extracting desired particles from a sample stream containing those
particles.
[0009] There are occasions in which a sample to be analyzed within
a microfluidic channel is of such a low concentration that it is
difficult, if not impossible, to get useful or reliable information
from the analyte. Thus, it is necessary to increase the
concentration of the sample to make it possible to get meaningful
results.
SUMMARY OF THE INVENTION
[0010] It is therefore an object of the present invention to
provide a device for increasing the concentration of a sample
flowing within a microfluidic channel.
[0011] It is a further object of the present invention to provide a
device which can reverse some of the dilution affects of an
H-Filter or similar device.
[0012] These and other objects of the present invention will be
more readily apparent from the descriptions and drawings that
follow.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] FIG. 1 is a top view of a T-Sensor which operates according
to the principles of the present invention; and
[0014] FIG. 2 is a top view of a diffusion channel of an H-Filter
which operates according to the principles of the present
invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0015] FIG. 1 shows a standard T-Sensor device, designated at 10,
the operation of which is described in detail in U.S. Pat. No.
5,716,852. T-Sensor 10 consists of a first channel 12 having an
input port 18. Channels 12 and 16 meet at a diffusion channel 20
having an output 21, as shown in FIG. 1. The characteristics of
T-Sensor 10 are such that fluids from channels 12 and 16 will flow
laminarly within diffusion channel 20.
[0016] To accomplish the desired concentration using T-Sensor 10, a
sample 22 to be concentrated, which contains constituents which
diffuse more slowly than the sample solvent molecules, is injected
into input port 14, while a concentrating solution 24 is injected
into port 18. The fluids flow through channels 12 and 16
respectively and finally into diffusion channel 20. Flow within
channel 20 is laminar such that a diffusion interface region 26 is
formed. Concentrating solution 24 is formulated such that is
extracts fluid from sample 22, and may contain large ionic
compounds, such as surfactant molecules, which do not diffusion
significantly into the sample stream, whereas sample fluid 22
molecules, typically small solvent molecules such as water, diffuse
into concentration solution 24 very quickly, as indicated by arrows
A, thus concentrating all molecules contained in sample 22 that
have a smaller diffusion coefficient (i.e., a larger size) than the
solvent molecules.
[0017] As an example, a sample solution of urine containing
bacteria is injected into port 14, while a concentrating solution
such as icodextrin is injected into port 18. Molecules from the
sample diffuse quickly into the icodextrin solution, and at output
21 of T-Sensor 10, the bacteria would be concentrated in a small
volume of fluid.
[0018] This process can be accelerated by providing a large
diffusion interface area, and a small diffusion distance. This is
shown in a patent application entitled "Microfluidic Device for
Rotational Manipulation of the Fluidic Interface between Multiple
Flow Streams," Ser. No. 09/956,497, filed Sep. 18, 2001; the
disclosure of which is incorporated by reference herein.
[0019] An alternative embodiment for carrying out the present
invention is shown in FIG. 2. Referring now to FIG. 2, the
diffusion channel 50 of an H-Filter structure is shown. The
velocity distribution of fluid flow in microchannels usually
follows a combination of a parabolic flow profile and a plug flow
profile, depending on viscosity, flow speed, channel dimensions,
etc. For a circular or square cross-sectional channel, the flow
profile is more or less uniformly parabolic, whereas for a
rectangular cross section, the flow profile is parabolic only in
the narrow dimension, and a combination of parabolic (close to the
walls) and plug flow (closer to the center of the channel), as
shown at 52 in FIG. 2.
[0020] If two fluids of similar viscosity flow parallel next to
each other in a T-Sensor or an H-Filter, such that one of the two
flows takes up only a narrow slice of the complete channel next to
a wall as seen at 54 in FIG. 2, then the average flow speed of this
flow will be lower than that of the other flow that takes up space
in the channel both in the center and on the other side of the
channel.
[0021] Separation by size in H-Filters and T-Sensors occurs because
the particles of different sizes initially contained in one of the
two flows diffuse across the fluid interface into the other flow at
different rates determined by the size of the particles. The
driving force for the diffusion is a concentration gradient present
between the two flows, which is initially very high, but, as
diffusion progresses, is reduced. This process is applicable to
both miscible and immiscible fluids.
[0022] If the average flow speed of the two flows is different,
i.e., if the bulk of the sample flows closer to the wall and
relatively slowly, while the bulk of the receiver solution flows
more in the center of the channel and relatively fast, then the
concentration of extracted molecules in the receiver solution is
increased more slowly, therefore increasing the effective diffusion
across the diffusion interface, and hence speeding up the
separation compared to an H-Filter in which both fluids flow at the
same rate.
[0023] This effect is frequently enhanced by having a sample with a
higher velocity than the receiver solution, thus further slowing
down the sample and increasing the separation speed. The separation
process can be further increased by providing a large diffusion
interface area and a small diffusion distance. In addition,
separation of fluids having different flow speeds by a permeable
membrane within a microchannel will also enhance diffusion across
the membrane.
[0024] While the present invention has been shown and described in
terms of a preferred embodiment thereof, it will be understood that
this invention is not limited to this particular embodiment and
that changes and modifications may be made without departing from
the true spirit and scope of the invention as defined in the
appended claims.
* * * * *