U.S. patent application number 09/985943 was filed with the patent office on 2003-10-23 for microfluidic flow control devices.
This patent application is currently assigned to Nanostream, Inc.. Invention is credited to Dantsker, Eugene, Karp, Christoph D., O'Connor, Stephen D..
Application Number | 20030196695 09/985943 |
Document ID | / |
Family ID | 22929445 |
Filed Date | 2003-10-23 |
United States Patent
Application |
20030196695 |
Kind Code |
A1 |
O'Connor, Stephen D. ; et
al. |
October 23, 2003 |
Microfluidic flow control devices
Abstract
Various microfluidic flow control devices are provided. In one
embodiment, a regulating device includes overlapping channel
segments separated by a deformable membrane in fluid communication
with one another. In another embodiment, a normally open
microfluidic valve provides latching valve operation with at least
one adhesive surface. A stencil-based microfluidic valve may be
operated by deforming a membrane against a seating surface to
prevent flow through an aperture. Configurable microfluidic devices
permit flow control among an interconnected microfluidic channel
network. Magnetic elements may be integrated into flexible
membranes to provide magnetically actuated microfluidic flow
control device.
Inventors: |
O'Connor, Stephen D.;
(Pasadena, CA) ; Karp, Christoph D.; (Pasadena,
CA) ; Dantsker, Eugene; (Sierra Madre, CA) |
Correspondence
Address: |
NANOSTREAM, INC.
580 SIERRA MADRE VILLA AVE.
PASADENA
CA
90071-2928
US
|
Assignee: |
Nanostream, Inc.
|
Family ID: |
22929445 |
Appl. No.: |
09/985943 |
Filed: |
November 6, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60246138 |
Nov 6, 2000 |
|
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|
Current U.S.
Class: |
137/87.01 |
Current CPC
Class: |
F16K 99/0051 20130101;
Y10T 137/87249 20150401; F16K 99/0055 20130101; Y10T 137/2559
20150401; Y10T 137/2496 20150401; B01L 2400/0638 20130101; B01L
2400/0487 20130101; F16K 99/0044 20130101; B01L 2300/14 20130101;
F16K 99/0046 20130101; B01L 3/50273 20130101; B01L 2400/0622
20130101; F16K 2099/0074 20130101; F16K 99/0001 20130101; B01L
3/5025 20130101; B01L 3/502707 20130101; B01L 3/502738 20130101;
B01L 2300/0874 20130101; F16K 2099/008 20130101; F16K 99/0061
20130101; F16K 99/0028 20130101; F16K 2099/0076 20130101; B01L
2300/0887 20130101; F16K 99/0015 20130101; B01L 2300/0816 20130101;
B01L 2300/123 20130101; Y10T 137/2663 20150401; B01L 2400/0655
20130101; B01L 2200/0689 20130101; F16K 2099/0078 20130101; F16K
99/0059 20130101; B01L 2400/0481 20130101 |
Class at
Publication: |
137/87.01 |
International
Class: |
G05D 011/00 |
Claims
What is claimed is:
1. A microfluidic regulating device comprising: a first channel
segment defined in a first layer of the device and containing a
fluid flow; a second channel segment defined in a second layer of
the device, the second channel segment being in fluid communication
with the first channel segment; and a membrane separating he first
channel segment and the second channel segment at a regulatory
region; wherein the presence of a pressure differential between the
first channel segment and the second channel segment causes the
membrane to deform toward and into the channel segment having a
lower internal pressure, thus reducing fluid flow capability
through the first channel segment or the second channel
segment.
2. The microfluidic regulating device of claim 1 wherein at least
one of the first device layer and the second device layer comprises
a sandwiched stencil layer.
3. The microfluidic regulating device of claim 1 wherein at least
one of the first device layer, the second device layer, and the
membrane has an adhesive surface.
4. The microfluidic regulating device of claim 1 wherein at least
one of the first device layer, the second device layer, and the
membrane comprises a self-adhesive tape material.
5. The microfluidic regulating device of claim 3 wherein, when a
pressure differential of sufficient magnitude is attained, the
deformable membrane contacts and is adhered to either the first
device layer or the second device layer.
6. The microfluidic regulating device of claim 1 wherein the
membrane is elastically deformable.
7. The microfluidic regulating device of claim 1 wherein the
membrane is a polymeric material selected from the group consisting
of polyesters, polycarbonates, polytetrafluoroethylenes,
polypropylenes, polyimides, polysilanes, polymethylmethacrylates,
and polyesters.
8. A microfluidic flow control device comprising: a first
microfluidic channel defined in a first stencil layer a valve
seating surface defining an aperture; a second microfluidic channel
defined in a second stencil layer, the second microfluidic channel
capable of fluid communication with the first microfluidic channel
through the aperture; and a deformable membrane substantially
centrally disposed above or below the aperture and capable of being
deformed to seal against the valve seating surface, thus preventing
fluid flow through the aperture; wherein fluid is permitted to flow
through the aperture when the deformable membrane is in an
undeformed state.
9. The microfluidic flow control device of claim 8 wherein at least
one of the deformable membrane and the valve seating surface has a
self-adhesive surface.
10. The microfluidic flow control device of claim 8, further
comprising a control channel bounded by the deformable membrane,
wherein pressure within the control channel may be manipulated to
deform the membrane.
11. A microfluidic flow control device comprising: a microfluidic
channel bounded from below by a lower surface and laterally by
channel walls; a first deformable membrane defining an upper
surface of the microfluidic channel, the first membrane capable of
being deformed into the microfluidic channel; and actuation means
capable upon activation of deforming the first membrane into the
microfluidic channel and into contact with the lower surface;
wherein at least one of the lower surface and the first membrane
has an adhesive surface capable of maintaining contact between the
lower surface and the first membrane after disactivation of the
actuation means.
12. The microfluidic flow control device of claim 11 further
comprising a stencil layer defining the channel walls that serve as
the lateral boundaries of the microfluidic channel, wherein the
lower surface is distinct from the stencil layer.
13. The microfluidic flow control device of claim 11 wherein the
lower surface comprises a second deformable membrane capable of
being deformed into the microfluidic channel.
14. The microfluidic flow control device of claim 11 wherein the
actuation means is selected from the group consisting of: manual,
mechanical, pneumatic, hydraulic, electric, magnetic, and
thermoelectric actuation.
15. The microfluidic flow control device of claim 11 wherein at
least one of the lower surface and the first membrane comprises a
self-adhesive tape material.
16. A microfluidic flow control device comprising: a first control
layer defining a plurality of first control layer channel segments;
a second control layer defining a plurality of second control layer
channel segments; a channel layer disposed between the first
control layer and the second control layer, the channel layer
defining a microfluidic channel network in fluid communication with
a plurality of inlet ports and a plurality of outlet ports; a first
membrane separating the first control layer and the channel layer
at a plurality of valve regions; and a second membrane separating
the second control layer and the channel layer at a plurality of
valve regions; wherein fluid flow paths between one or more
specific inlet ports and one or more specific outlet ports may be
selectively established by manipulating the pressure within
individual control layer channel segments to cause deformation of
the first membrane and/or the second membrane toward and into the
channel network at one or more valve regions.
17. The microfluidic flow control device of claim 16 wherein at
least one of the first control layer, the second control layer, and
the channel layer comprises a stencil layer.
18. The microfluidic flow control device of claim 16 wherein at
least one of the first control layer, the second control layer, the
channel layer, the first membrane, and the second membrane has an
adhesive surface.
19. The microfluidic flow control device of claim 16 wherein the
first membrane or the second membrane comprises a plurality of
different membrane materials to provide different valve
characteristics at specific valve regions.
20. The microfluidic flow control device of claim 16 wherein the
plurality of first control layer channel segments are oriented
substantially orthogonal to the plurality of second control layer
channel segments.
21. A microfluidic flow control system comprising the microfluidic
flow control device of claim 16 and at least one pressure
source.
22. The microfluidic flow control system of claim 21 further
comprising a controller for controlling pressure within individual
channel segments.
23. The microfluidic flow control system of claim 22, wherein
particular fluid flow paths may be selectively programmed via the
controller.
24. The microfluidic flow control system of claim 22 further
comprising a sensor, wherein the controller receives a feedback
signal from the sensor.
25. A microfluidic flow control device comprising: a first
microfluidic channel; a second microfluidic channel capable of
being in fluid communication with the first microfluidic channel;
at least one deformable membrane capable of affecting fluid flow
between the first microfluidic channel and the second microfluidic
channel; at least one magnetic element associated with the at least
one deformable membrane; wherein application of a magnetic field
deforms the at least one deformable membrane.
26. The microfluidic flow control device of claim 25 wherein the at
least one magnetic element is bound to or laminated within the at
least one deformable membrane.
27. The microfluidic flow control device of claim 25 wherein the at
least one magnetic element comprises a discrete magnetic
element.
28. The microfluidic flow control device of claim 26 wherein the at
least one magnetic element defines a first aperture, the at least
one membrane defines a second aperture, and deformation of the
membrane selectively permits fluid to flow through the first
aperture and the second aperture.
29. The microfluidic flow control device of claim 25 further
comprising a valve seating surface, wherein the membrane may
selectively contact the seating surface.
30. A microfluidic flow control system comprising: the microfluidic
flow control device of claim 25; and at least one magnetic field
generator.
31. The microfluidic flow control system of claim 30 wherein the at
least one magnetic field generator includes a field concentrating
element.
32. The microfluidic flow control system of claim 30, further
comprising a controller for controlling the at least one magnetic
field generator.
33. The microfluidic flow control system of claim 32 wherein the
controller is programmable.
34. The microfluidic flow control system of claim 32, further
comprising a sensor, wherein the controller receives a feedback
signal from the sensor.
35. The microfluidic flow control system of claim 34 wherein the
system functions to regulate pressure or fluid flow within at least
a portion of the microfluidic device.
36. The microfluidic flow control system of claim 32, wherein the
at least one field generator comprises a plurality of field
generators each having an associated field concentrating element,
and wherein the at least one magnetic element comprises a plurality
of discrete magnetic elements.
37. The microfluidic flow control system of claim 36, further
comprising a plurality of fluidic inlet ports and a plurality of
fluidic outlet ports, wherein fluid flow paths between one or more
specific inlet ports and one or more specific outlet ports may be
selectively established.
38. A configurable microfluidic device comprising: a network of
interconnected microfluidic channels; a plurality of first control
channels; a plurality of second control channels; wherein the first
control channels and the second control channels are separated by
one or more deformable membranes from the network of interconnected
microfluidic channels at one or more regulatory regions.
39. The configurable microfluidic device of claim 38, further
comprising a control system for controlling the pressure in said
first control channels and in said second control channels.
Description
STATEMENT OF RELATED APPLICATION(S)
[0001] This application claims benefit of U.S. application Ser. No.
60/246,138, filed on Nov. 6, 2000.
FIELD OF THE INVENTION
[0002] The present invention relates to microfluidic devices and
the control of fluid flow within those devices.
BACKGROUND OF THE INVENTION
[0003] There has been a growing interest in the manufacture and use
of microfluidic systems for acquiring chemical and biological
information. In particular, when conducted in microfluidic volumes,
complicated biochemical reactions may be carried out using very
small volumes of liquid. Among other benefits, microfluidic systems
increase the response time of reactions, minimize sample volume,
and lower reagent consumption. When volatile or hazardous materials
are used or generated, performing reactions in microfluidic volumes
also enhances safety and reduces disposal quantities.
[0004] Traditionally, microfluidic systems have been constructed in
a planar fashion using techniques borrowed from the silicon
fabrication industry. Representative systems are described, for
example, in some early work by Manz et al. (Trends in Anal. Chem.
(1990) 10(5): 144-149; Advances in Chromatography (1993) 33: 1-66).
These publications describe the construction of microfluidic
devices using photolithography to define channels on silicon or
glass substrates and etching techniques to remove material from the
substrate to form the channels. A cover plate is bonded to the top
of the device to provide closure.
[0005] More recently, a number of methods have been developed that
allow microfluidic devices to be constructed from plastic, silicone
or other polymeric materials. In one such method, a negative mold
is first constructed, and then plastic or silicone is poured into
or over the mold. The mold can be constructed using a silicon wafer
(see, e.g., Duffy et al., Analytical Chemistry (1998) 70:
4974-4984; McCormick et. al., Analytical Chemistry (1997) 69:
2626-2630), or by building a traditional injection molding cavity
for plastic devices. Some molding facilities have developed
techniques to construct extremely small molds. Components
constructed using a LIGA technique have been developed at the
Karolsruhe Nuclear Research center in Germany (see, e.g., Schomburg
et al., Journal of Micromechanical Microengineering (1994) 4:
186-191), and commercialized by MicroParts (Dortmund, Germany).
Jenoptik (Jena, Germany) also uses LIGA and a hot-embossing
technique. Imprinting methods in polymethylmethacrylate (PMMA) have
also been demonstrated (see, e.g., Martynova et aL, Analytical
Chemistry (1997) 69: 4783-4789). However, these techniques do not
lend themselves to rapid prototyping and manufacturing flexibility.
Moreover, the tool-up costs for such techniques are quite high and
can be cost-prohibitive.
[0006] Typically, flow control within microfluidic devices has been
provided through the application of electric currents to cause
electrokinetic flow. Systems for providing such utility are
complicated and require electrical contacts to be present.
Additionally, such systems only function with charged fluids, or
fluids containing electrolytes. Finally, these systems require
voltages that are sufficiently high as to cause electrolysis of
water, thus forming bubbles that complicate the collection of
samples without destroying them. Therefore, there exists a need for
a microfluidic device capable of controlling flow of a wide variety
of fluids without using electrical currents.
[0007] Some of the basic challenges involved in operating
microfluidic systems result from attempts to interface between
conventional "macro-scale" devices and microfluidic components. Due
to the very small cross-sectional area of microfluidic channels,
flow through these channels can be quite sensitive to pressure
variations. Assuming that an external pressure source is used to
motivate fluid flow in a microfluidic system, a number of
applications would benefit if the flow rate of a flowing fluid
could be controlled in spite of variations in input pressure. For
example, such control can be especially valuable in performing
reactions such as chemical or biological synthesis. To reduce
overall costs and provide versatility, it would be desirable to
achieve controlled fluid flow within a microfluidic device using
various low-precision pressure sources, such as, for example, a
conventional manually-operated syringe or an inexpensive,
low-precision syringe pump. Also in the interest of reducing costs,
it would be desirable to provide controlled fluid flow in a
microfluidic device with a minimum of moving parts or control
components. Thus, there exists a need for a simple yet robust
microfluidic regulating device capable of receiving fluid from a
low-precision source and providing a controlled fluid flow rate in
spite of fluctuations in input pressure.
[0008] A microfluidic device with limited (i.e., on-off) flow
control capability is provided in U.S. Pat. No. 5,932,799 to Moles
("the Moles '799 patent"). There, polyimide layers enhanced with
tin (between 400-10,000 ppm) are surface micromachined (e.g.,
etched) to form recessed channel structures, stacked together, and
then thermally bonded without the use of adhesives. A thin,
flexible valve member actuated by selective application of
positively or negatively pressurized fluid selectively enables or
disables communication between an inlet and an outlet channel. The
valve structure disclosed in the Moles '799 patent suffers from
numerous drawbacks that limit its utility, however. First, the
valve is limited to simple on-off operation requiring a constant
actuation signal, and is incapable of regulating a constant flow.
Second, the valve is normally closed in its unactuated state. It is
often desirable in microfluidic systems to provide normally open
valve structures subject to closure upon actuation. Third, the
Moles '799 patent teaches the fabrication of channels using
time-consuming surface micromachining techniques, specifically
photolithography coupled with etching techniques. Such
time-consuming methods not only require high setup costs but also
limit the ability to generate, modify, and optimize new designs.
Fourth, the Moles '799 patent teaches only fabrication of devices
using tin-enhanced polyimide materials, which limits their utility
in several desirable applications. For example, polyimides are
susceptible to hydrolysis when subjected to alkaline solvents,
which are advantageously used in applications such as chemical
synthesis. The inclusion of tin in the device layers may present
other fluid compatibility problems. Finally, polyimides are
generally opaque to many useful light spectra, which impedes their
use with common detection technologies, and further limits
experimental use and quality control verification.
[0009] Another microfluidic valve structure having limited utility
is disclosed in WIPO International Publication Number WO 99/60397
to Holl, et al. There, a microfluidic channel is bounded from above
by a thick, deformable elastic seal having a depressed region that
protrudes through an opening above the channel. An actuated
external valve pin presses against the elastic seal, which is
extruded through the opening into the channel in an attempt to
close the channel. This valve, however, suffers from defects that
limit its utility. To begin with, it is difficult to fabricate an
elastic seal having a depressed region to precisely fit through the
opening above the channel without leakage. Additionally, the valve
provides limited sealing utility because it is difficult to ensure
that the extruded seal completely fills the adjacent channel,
particularly in the lower corners of the channel. Further, the
contact region between the external valve pin and the elastic seal
is subject to frictional wear, thus limiting the precision and
operating life of the valve.
[0010] Using conventional technologies, it is generally difficult
to quickly generate and modify designs for robust microfluidic
devices. To include flow control capability in such a device only
elevates that difficulty. It would be desirable to provide a
"generic" microfluidic platform that could be quickly and easily
tuned with various components and/or materials to provide different
flow control utilities depending on the particular application,
taking into account varying design criteria such as the operating
fluid, the flow rates, and the pressures involved. If available,
such a platform would promote rapid prototyping and device
optimization at a substantially reduced cost compared to
conventional technologies.
[0011] Additionally, it would be desirable to enable flow through a
microfluidic channel network to be externally controlled without
the attendant drawbacks of electrokinetic or electrophoretic flow.
In particular, it would be desirable to provide a channel network
having multiple inlets and multiple outlets, and be able to
selectively establish fluid flow paths through the network between
one or more specific inlets and one or more specific outlets. If
available, such a device could be used as a versatile fluid
"switch." It would be particularly desirable if this fluid
switching utility could be externally programmed so as to execute
repetitive and/or sequential functions with minimal user
interaction. Preferably, a fluid switching device or system would
be simple and robust with a minimum number of parts subject to
wear.
[0012] Finally, conventional "on-off" microfluidic valve structures
such as the valve disclosed in the Moles '799 reference require
constant application of a control signal, thus consuming external
actuation resources for as long as a valve state is to be
maintained. To reduce the consumption of external actuation
resources and provide other capabilities including fluid logic
functions, it would be desirable to provide robust microfluidic
valves with "latching" capability, in other words, the ability to
maintain position in an actuated state without continuous
application of an actuation signal. These and other needs and
desirable aspects are addressed herein.
SUMMARY OF THE INVENTION
[0013] In a first separate aspect of the invention, a microfluidic
regulating device includes a first and a second channel segment
defined in different layers of a microfluidic device and in fluid
communication with one another. A membrane separates the channel
segments at a regulatory region. In the presence of a pressure
differential between the two channel segments, the membrane is
deformed toward and into the channel segment having a lower
internal pressure, thus reducing fluid flow capability through the
first or the second channel segment.
[0014] In another separate aspect of the invention, a normally open
microfluidic flow control device includes a first and a second
microfluidic channel each defined in different stencil layers.
Fluid communication may be established between the first and the
second channel through an aperture defined in a valve seating
surface. A deformable membrane centrally disposed above or below
the aperture is capable of being deformed to seal against the valve
seating surface, thus preventing fluid flow through the
aperture.
[0015] In another separate aspect of the invention, a microfluidic
flow control device includes a microfluidic channel bounded by a
lower surface, by lateral channel walls, and by a deformable
membrane capable of being deformed by actuation means into the
channel and against the lower surface. At least one of the lower
surface and the first membrane has an adhesive surface capable of
maintaining contact between the lower surface and the first
membrane after disactivation of the actuation means.
[0016] In another separate aspect of the invention, a microfluidic
flow control device includes a first control layer and a second
control layer each defining multiple channel segments. A channel
layer, which defining a microfluidic channel network in fluid
communication with multiple fluid inlet ports and fluid outlet
ports, is disposed between the first and the second control layer.
A flexible membrane separates the first control layer and the
channel layer, and a flexible membrane separates the second control
layer and the channel layer. Fluid flow paths between one or more
specific inlet ports and one or more specific outlet ports may be
selectively established by manipulating pressure within individual
control channels, thus causing deformation of the first and/or the
second membrane into the channel network at one or more valve
regions.
[0017] In another separate aspect of the invention, a microfluidic
flow control device includes a first and a second microfluidic
channel capable of being in fluid communication, and a deformable
membrane capable of affecting fluid flow between the two channels.
A magnetic element is associated with the deformable membrane.
Application of a magnetic field deforms the deformable
membrane.
[0018] In another separate aspect of the invention, a configurable
microfluidic device includes a network of interconnected fluid
channels and multiple first and second control channels. The first
and second control channels are separated from the network of
interconnected microfluidic channels by at least one deformable
membrane at one or more regulatory regions.
[0019] In another aspect of the invention, any of the foregoing
separate aspects may be combined for additional advantage.
[0020] These and other aspects and advantages of the present
invention will become apparent from the following detailed
description of the preferred embodiments taken in conjunction with
the figures.
BRIEF DESCRIPTION OF THE DRAWINGS
[0021] FIGS. 1A-1C are cross-sectional views of at least a portion
of microfluidic device constructed from 5 layers of material, the
device having a deformable membrane separating equally-sized upper
channel region and a lower channel region. FIG. 1A illustrates the
membrane in a neutral position. FIG. 1B illustrates the membrane
being deflected toward and into the lower channel region. FIG. 1C
illustrates the membrane being deflected toward and into the upper
channel region.
[0022] FIGS. 2A-2B are cross-sectional views of at least a portion
of a 5-layer microfluidic device having a larger upper channel
region and a smaller lower channel region. FIG. 2A illustrates the
membrane being deformed toward and into the smaller, lower channel
region. FIG. 2B illustrates the membrane being deformed toward and
into the larger, upper channel region.
[0023] FIGS. 3A-3E are cross-sectional views of at least a portion
of a microfluidic device having three separate channel regions (an
upper, a central, and a lower channel region) divided by two
deformable membranes (an upper and a lower membrane). FIG. 3A
illustrates both membranes in neutral positions. FIG. 3B
illustrates the upper deformable membrane being deflected toward
and into the central channel region. FIG. 3C illustrates both the
upper and the lower deformable membrane being deflected toward and
into the central channel region. FIG. 3D illustrates the lower
deformable membrane being deflected toward and into the central
channel region. FIG. 3E illustrates both the upper and lower
deformable membrane being deflected away from the central channel
region, namely, the upper deformable membrane being deflected
toward and into the upper channel region, and the lower deformable
membrane being deflected toward and into the lower channel
region.
[0024] FIG. 4A is an exploded perspective view of a five-layer
microfluidic device having a pressure-activated regulating valve
that controls fluid flow within the device. FIG. 4B is a top view
of the assembled device of FIG. 4A.
[0025] FIG. 5A is a top view of a portion of one layer of at least
a portion of a microfluidic device, the layer having a network of
interconnected channels. FIG. 5B is a top view of portions of two
additional, superimposed layers of the same device shown in FIG.
5A, the two additional layers defining control channels for
directing fluid flow within the channel network illustrated in FIG.
5A. FIG. 5C is a top view of a membrane that may be used in the
device illustrated in FIGS. 5A-5B, the membrane composed of
different membrane materials in four regions. FIG. 5D is a top view
of a membrane similar to the membrane illustrated in FIG. 5C, but
composed of different membrane materials in sixteen regions. FIG.
5E is a top view of the superimposed layer portions of FIGS. 5A-5B
and two membranes assembled into a microfluidic device, with
schematic illustration of the device being operated to define one
possible fluid flow path. FIG. 5F is a schematic illustration of a
microfluidic flow control system including the microfluidic device
of FIG. 5E coupled to at least one pressure source and a
controller, among other components.
[0026] FIG. 6A is an exploded perspective view of a five-layer
microfluidic device capable of delivering a relatively constant
flow rate of fluid over a large range of pressures. FIG. 6B is a
top view of the assembled device of FIG. 6A. FIG. 6C is a
cross-sectional view of a portion of the microfluidic device of
FIGS. 6A-6B along section lines "A-A" shown in FIG. 6B, with the
regulatory region in the open position. FIG. 6D provides the same
cross-sectional view as FIG. 6C, but with the regulatory region in
the closed position.
[0027] FIG. 6E is a chart showing the flow rates achieved at the
unregulated and regulated outlets of the device shown in FIGS.
6A-6D over a range of input pressures, with each outlet tested
separately while the other outlet was sealed. FIG. 6F is a chart
showing the flow rates at both the unregulated and regulated
outlets of the device shown in FIGS. 6A-6D over a range of input
pressures, measured with both outlets open.
[0028] FIG. 7A is a cross-sectional view of a portion of a
microfluidic device having three channel segments that meet at a
regulatory region and that are separated by a single deformable
membrane. FIG. 7B provides the same cross-sectional view as FIG.
7A, but with the membrane deflected toward and into the upper
channel segment.
[0029] FIG. 8A is a cross-sectional view of a deformable membrane
having a magnetic element affixed to the membrane. FIG. 8B is a
cross-sectional view of a deformable membrane formed with two
membrane layers laminated around a magnetic element. FIG. 8C is a
cross-sectional view of a deformable membrane formed with a central
magnetic element, two outer membrane layers and a central stencil
layer.
[0030] FIG. 9A is a cross-sectional view of a magnetic field
generating element microfluidic flow control device and at least a
portion of a microfluidic flow control device having a magnetic
element laminated within a membrane layer, the membrane being in a
relaxed state. FIG. 9B provides the same cross-sectional view as
FIG. 9A, but with the membrane in a deformed state to prevent flow
between two microfluidic channels within the flow control
device.
[0031] FIG. 10 is a perspective view of a magnetic field generator
array disposed above a microfluidic flow control device having
multiple fluid inlets and outlets and multiple magnetic elements
associated with flexible membranes to provide flow control
utility.
[0032] FIG. 11 is a schematic illustration of a microfluidic flow
control system showing interconnections between a microfluidic flow
control device, a magnetic field generator array, and a controller,
among other components.
[0033] FIG. 12A is a cross-sectional view of at least a portion of
a microfluidic device having a deformable membrane disposed above
an aperture permitting fluid communication between two channels.
FIG. 12B provides the same cross-sectional view as FIG. 12A, but
with the membrane deformed to seal the aperture and prevent fluid
communication between the two channels.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS OF THE INVENTION
[0034] Definitions
[0035] The term "channel" as used herein is to be interpreted in a
broad sense. Thus, it is not intended to be restricted to elongated
configurations where the transverse or longitudinal dimension
greatly exceeds the diameter or cross-sectional dimension. Rather,
the terms are meant to include cavities, tunnels, or chambers of
any desired shape or configuration through which liquids may be
directed. Such a fluid cavity may, for example, comprise a
flow-through cell where fluid is to be continually passed or,
alternatively, a chamber for holding a specified, discrete amount
of fluid for a specified amount of time. "Channels" may be filled
or may contain internal structures comprising valves or equivalent
components.
[0036] The term "channel segment" as used herein refers to a region
of a channel.
[0037] A "change in channel segment shape and geometry" indicates
any change in the dimensions of a channel segment. For instance,
the channel segment can become smaller, larger, change shape, be
completely closed, be partially closed, be permanently restricted,
etc.
[0038] The term "microfluidic" as used herein is to be understood,
without any restriction thereto, to refer to structures or devices
through which fluid(s) are capable of being passed or directed,
wherein one or more of the dimensions is less than 500 microns.
[0039] The term "stencil" as used herein refers to a material layer
that is preferably substantially planar, through which one or more
variously shaped and oriented portions has been cut or otherwise
removed through the entire thickness of the layer, and that permits
substantial fluid movement within the layer (e.g., in the form of
channels or chambers, as opposed to simple through-holes for
transmitting fluid through one layer to another layer). The
outlines of the cut or otherwise removed portions form the lateral
boundaries of microstructures that are formed upon sandwiching a
stencil between substrates and/or other stencils.
[0040] Fabrication of Microfluidic Devices
[0041] Microfluidic devices providing flow control utility
according to the present invention may be fabricated in various
ways using a wide variety of materials. In an especially preferred
embodiment, microfluidic devices according to the present invention
are constructed using stencil layers to define channels and/or
chambers. As described in further detail in co-pending U.S.
application Ser. No. 09/453,029 filed Dec. 1, 1999, which is hereby
incorporated by reference as if fully set forth herein, a stencil
layer is preferably substantially planar and has microstructure cut
through the layer. For example, a computer-controlled plotter
modified to accept a cutting blade may be used to cut various
patterns through a material layer. Alternatively, a
computer-controlled laser cutter may be used. As further
alternatives, conventional stamping, cutting, and/or molding
technologies may be employed to form stencil layers. The wide
variety of materials that may be used to fabricate microfluidic
devices using sandwiched stencil layers include polymeric,
metallic, and/or composite materials, to name a few. Notably, use
of stencil-based fabrication methods enables a particular device
design to be rapidly "tuned" or optimized for particular operating
parameters, since different material types and thicknesses may be
readily used and/or substituted for individual layers within a
device. The ability to prototype devices quickly with stencil
fabrication methods permits many different variants of a particular
design to be tested and evaluated concurrently.
[0042] When assembled in a microfluidic device, the top and bottom
surfaces of stencil layers may mate with one or more adjacent
stencil or substrate layers to form a substantially enclosed
device, typically having one or more inlet ports and one or more
outlet ports. In one embodiment, one or more layers of a device are
comprised of single- or double-sided adhesive tape, although other
methods of adhering stencil layers may be used. A portion of the
tape (of the desired shape and dimensions) can be cut and removed
to form channels, chambers, and/or apertures. A tape stencil can
then be placed on a supporting substrate, between layers of tape,
or between layers of other materials. In one embodiment, stencil
layers can be stacked on each other. In this embodiment, the
thickness or height of the channels can be varied by varying the
thickness of the stencil (e.g., the tape carrier and the adhesive
material thereon) or by using multiple substantially identical
stencil layers stacked on top of one another. Various types of tape
are useful with this embodiment. Suitable tape carrier materials
include but are not limited to polyesters, polycarbonates,
polytetrafluoroethlyenes, polypropylenes, and polyimides. Such
tapes may have various methods of curing, including curing by
pressure, temperature, or chemical or optical interaction. The
thicknesses of these carrier materials and adhesives may be
varied.
[0043] Alternatively, microfluidic devices according to the present
invention are fabricated from materials such as glass, silicon,
silicon nitride, quartz, or similar materials. Various conventional
machining or micromachining techniques such as those known in the
semiconductor industry may be used to fashion channels, vias,
and/or chambers in these materials. For example, techniques
including wet or dry etching and laser ablation may be used. Using
such techniques, channels, chambers, and/or apertures may be made
into one or more surfaces of a material or penetrate through a
material.
[0044] Still further embodiments may be fabricated from various
materials using well-known techniques such as embossing, stamping,
molding, and soft lithography.
[0045] In addition to the use of adhesives or single- or
double-sided tape discussed above, other techniques may be used to
attach one or more of the various layers of microfluidic devices
useful with the present invention, as would be recognized by one of
ordinary skill in attaching materials. For example, attachment
techniques including thermal, chemical, or light-activated bonding;
mechanical attachment (such as using clamps or screws to apply
pressure to the layers); or other equivalent coupling methods may
be used.
[0046] Microfluidic Membrane Valves
[0047] In various embodiments of the present invention, membranes
are used in microfluidic devices to provide flow control utility.
In one embodiment, a microfluidic device includes a first
microfluidic channel segment and a second microfluidic channel
segment that are separated by a deformable membrane at a regulatory
region. The channels may be defined in horizontal layers of a
device, with the deformable membrane forming a separate horizontal
layer separating the channel layers. The channels can overlap at
any suitable angle. The channels may be orthogonal, thus limiting
the area of the overlap region, or they may be substantially
parallel. The first and second channels also can be in fluid
communication. Where the channels are in fluid communication, the
use of the terms first channel segment and second channel segment
refer to regions forming a channel disposed on different layers of
the device. A change in relative pressure between the first and
second channels results in deformation of the membrane separating
the channels. The membrane is deformed towards the channel segment
with lower relative pressure. The membrane can partially block flow
of the fluid through the channel segment with lower relative
pressure or can substantially block flow of the fluid through the
channel segment with lower relative pressure. The degree of
deformation of the deformable membrane is related to the
differential pressure between the first and second channels.
Generally, the greater the differential pressure, then the greater
the observed deformation of the deformable membrane.
[0048] FIGS. 1A-1C illustrate at least a portion of a microfluidic
device 90 having a deformable membrane 102 that is responsive to
changes in pressure between two channel segments 105, 106. The
channel segments 105, 106 may be defined in stencil layers 101, 103
disposed between outer layers 100, 104. The deformable membrane 102
separates the first channel segment 105 defined in layer 101 from
the second channel segment 106 defined in layer 103. When the
pressures in channels 105 and 106 are substantially the same, then
the deformable membrane 102 adopts a neutral position, as shown in
FIG. 1A. If the pressure in channel segment 105 is increased, or
the pressure in channel segment 106 substantially decreased, then
the deformable membrane 102 will deform towards channel segment
106, as shown in FIG. 1B. When a sufficient differential pressure
is attained, the deformable membrane 102 (specifically the lower
surface 107 of the membrane 102) may contact the upper surface 108
of the outer layer 104. When the pressure in channel segment 106 is
substantially increased or that in channel segment 105
substantially decreased, the deformable membrane 102 may deform
into the channel segment 105, as shown in FIG. 1C. When a
sufficient differential pressure is attained, the deformable
membrane 102 (specifically, the upper surface 109) will contact the
lower surface 110 of substrate layer 100.
[0049] As noted previously, the channel segment-containing portion
of the device 90 can be constructed using any suitable materials,
by any suitable technique. In a particularly preferred embodiment,
a microfluidic device is constructed with sandwiched stencil
layers. The layers of the device containing channel segments may
also be constructed from etched silicon, molded polymers, or using
other materials or fabrication methods known to one skilled in the
art of making microfluidic devices. For example, in the device 90
illustrated in FIGS. 1A-1C, the channel segment 105 could be
surface etched into a single integral substrate substituted for
separate layers 100 and 101. Likewise, channel segment 106 could be
etched into a single integral substrate substituted for separate
layers 103 and 104.
[0050] Microfluidic devices described herein may be constructed
using still further techniques. In certain embodiments, channels
are constructed in materials using etching, embossing, or molding
techniques. Two or more different elements may be constructed.
Then, the multiple elements may be assembled face-to-face with a
deformable membrane disposed between them. The channels in the two
etched or embossed devices may overlap in certain areas of the
completed device with the deformable intermediary layer between the
channel segments. Additionally, one or more apertures may be
defined in the intermediate layer to serve as vias connecting the
channels in the upper and lower devices. More complicated systems
can be constructed.
[0051] Control of the properties of the microfluidic device can be
achieved by varying the deformable membrane material. The material
can be elastically deformable or can be inelastically deformable.
Suitable membrane materials include papers, foils and polymers. In
a preferred embodiment, the membrane is a polymer including, for
example, polyesters, polycarbonates, polytetrafluoroethylenes,
polypropylenes, polyimides (e.g., KAPTON.RTM.) and polyesters
(e.g., MYLAR.RTM.), silanes (e.g., PDMS) and polymethylmethacrylate
(PMMA). A more rigid material will deflect less readily due to a
change in pressure, while a more malleable material will deflect
more easily. A membrane material also can be chosen based on its
ability to perform repeated deformation cycles.
[0052] The sensitivity of microfluidic device to changes in
differential pressure may also be controlled by varying the
thickness of the deformable membrane. Generally, a thinner membrane
material will be more easily deformed and will respond more easily
to changes in differential pressure. A thicker membrane will
generally be less easily deformed and will be less sensitive to
changes in relative pressure. The thickness or height of the
channel segment into which the deformable channel segment moves
also will impact the fluid control performance of the system.
[0053] Another technique for adjusting the sensitivity of the
microfluidic system to changes in relative pressure is to change
the area of the regulatory region or deformable membrane. Adjacent
microfluidic channels or chambers separated by a deformable
membrane may be fashioned in a wide variety of sizes, shapes, and
geometries. Channel or chamber segments can overlap in a
perpendicular format, at an angle or along a length of channel
segment that is parallel. Channels within a regulator region may be
formed with constant widths or variable widths. One example of a
regulatory region is provided in FIGS. 6A-6B, in which the
regulatory region 207 is circular.
[0054] The areas of adjacent channel segments opposite the membrane
at the regulatory region may also be different from one another.
The larger the deformable membrane, for example, the more easily it
provide substantially complete blockage of fluid flow in the
adjacent channel segment. FIGS. 2A-2B show at least a portion of a
microfluidic device 299 having, at the valve location, a relatively
large channel segment 305 and a smaller channel segment 306
separated by deformable membrane 302. When the relative pressure in
the larger channel segment 305 is higher than that in the smaller
channel segment 306, the membrane 302 in the valve region deforms
toward and into the smaller channel segment 306, as shown in FIG.
2A. The small relative size of channel segment 306 means that the
deformable membrane 302 only reduces the available cross section of
channel segment 306 to about half its original size. However, when
the relative pressure in channel segment 306 is higher than the
pressure in channel segment 305, then the membrane 302 deforms
toward and into the larger channel segment 305, as shown in FIG.
2B. Because of the relatively large area of the channel 305 bounded
by the deformable portion of the membrane 302, the membrane 302 is
able to move more easily into channel segment 305, thereby
significantly changing the cross section of the channel segment
305. For example, a membrane having a deformable portion 5 mm in
diameter will deflect across a 3-mil (75 microns) channel segment
more readily than a 2 mm diameter deformable membrane portion,
because there is less of a percentage of deformation of the larger
membrane.
[0055] In a preferred embodiment, a channel subject to fluidic
control defines an aperture opposite and substantially aligned with
the center of a deformable membrane. In such a configuration, a
fluid flow path is provided in a direction parallel to the
direction of travel of the deformable membrane. For example, FIG.
6C shows at least a portion of a microfluidic device having a
channel segment 207 in fluid communication with an aperture 210
aligned substantially centrally below the deformable membrane 202.
Deformation of the membrane 202 towards channel segment 207 results
in substantially complete blockage of fluid flow between channel
segments 210 and 207. While similar devices can be constructed with
the aperture disposed in various positions relative to the path of
the deformable membrane, it is highly preferable to position the
aperture near to the center of travel of the deformable a membrane
to promote substantial blockage of the fluid flow path by the
membrane. The size of the aperture will also affect the amount of
pressure required to provide substantially leak-free sealing.
[0056] Using these techniques, a system can be constructed in which
deformation of the material results in either partial blockage or
substantially complete blockage of fluid flow through a channel
segment. An elastic material may be used where reversible control
of fluid flow is desired. Lowering the pressure in the higher
relative pressure channel segment allows the deformable membrane to
resume its neutral state, allowing unrestricted fluid flow. In
certain applications, it is desirable to provide substantially
permanent or irreversible change to a microfluidic channel segment.
For example, it may be desirable for a system to provide shut-off
valving utility to protect downstream components from damage caused
by high flow or pressure. Upon increase in pressure in one channel
segment, an inelastic material will be plastically deformed towards
the channel segment with lower pressure. The material will remain
substantially in the deformed position. Such results may be
obtained with semi-malleable materials including suitable metal
foils.
[0057] A deformable membrane also can be made of materials with
surface properties that alter its behavior. For example, a membrane
can be tacky or have an adhesive coating. Such properties or
coatings can be applied to one or both sides of the deformable
membrane. Depending on the strength of the adhesive or degree of
tackiness, the deformable membrane can operate as a variable
switch. At low relative pressures, the membrane can act
elastically. At high pressures, or for systems designed for the
deformable membrane to physically contact the opposing wall of the
adjacent channel segment, the deformation can result in permanent
or semi-permanent closure of the adjacent channel segment. In
another embodiment, the membrane used can be non-adhesive, but the
surface against which it seals can be constructed with a tacky or
adhesive surface. For example, in FIG. 1B, the lower surface 107 of
the deformable membrane 101 can be coated with an adhesive, or can
be constructed from an adhesive tape, such that upon deformation
sufficient to provided contact between the membrane 102 and the
lower layer 104, the deformable membrane 102 can be affixed to the
upper surface 108 of the lower layer 104. The degree of permanence
of the closure depends on factors including elasticity of the
membrane and the strength of the adhesive material used. Similar
results can be achieved by coating the upper surface 108 with
adhesive or both surfaces 107 and 108 with adhesive, or by forming
one or more of these surfaces from single- or double-sided
self-adhesive tape materials. Referring to FIG. 1B, the bottom
surface of the membrane 107 or the upper surface 108 of the bottom
layer 104 may include permanent or semi-permanent adhesives. When
the membrane 102 is deformed, such as by an elevated pressure
within the upper chamber 105, then the membrane 102 may be deformed
to contact the lower layer 104 to permit the adhesive to bind the
surfaces together and permanently or semi-permanently obstruct the
lower channel segment 106.
[0058] In certain embodiments, the membrane 102 may be deformed and
adhered to the lower surface in a semi-permanent manner that may be
reversed by further manipulation. For example, when pressure is
applied to 105, the membrane 102 is deformed so as to the contact
the lower layer 104, where the membrane 102 and the upper surface
108 of the lower layer 104 are adhesively bound. Alternatively, the
membrane 102 may be plastically deformed into the lower channel
106. When the pressure is re-equalized between the upper and lower
chambers 105, 106, the membrane 102 will remain affixed to the
lower layer 104 until sufficient pressure is applied to channel
segment 106 to overcome the adhesive bond or plastic deformation of
the membrane 102. In many cases, the pressure required to
reposition (i.e., re-deform) the membrane 102 may be greater than
the pressure to originally deform it.
[0059] In another embodiment, a microfluidic valve may include two
microfluidic channels separated by a seating surface defining an
aperture for mating with a deformable membrane to provide flow
control utility. For example, FIGS. 12A-12B illustrate a
microfluidic device 197 fabricated from seven layers 200-204, 220,
221 and having a control channel 205 bounded in part by a
deformable membrane 202. With the deformable membrane in a relaxed,
neutral state, fluid flow may be established between a first
channel 207 and a second channel 222 defined in different layers
203, 220 of the device 197 and separated by a seating layer 204
defining an aperture 210. The deformable membrane 202 is disposed
substantially centrally above the aperture 210 to promote tight
sealing of the aperture when the control channel 205 is pressurized
to deform the membrane 202 to contact the seating layer 204, as
shown in FIG. 12B. The valve seating layer 210 adjacent to the
aperture 210 may be considered a valve seating surface. The device
197 thus serves as a normally open valve that permits flow through
the aperture when the deformable membrane is in an undeformed
state. Selective pressurization of the control channel 205 permits
closure of the valve. Either or both of the membrane 202 and the
seating layer 204 may be provided with an adhesive surface to
provide latching valve utility.
[0060] In further embodiments, more complex fluid control
structures utilizing multiple membranes may be formed. For example,
more than two channels can meet at a valve region separated by one
or more membranes. In certain embodiments, more than one pressure
regulator may be stacked in a given vertical position of a
microfluidic device. In one embodiment, three channels overlap at a
single valve region, with two deformable membranes separating the
various channels. FIGS. 3A-3E show five cross-sectional views of
such an overlap. FIG. 3A shows a cross-section of at least a
portion of a microfluidic device 119 formed using sandwiched
stencils, the device having seven layers 120-126 and forming three
channel segment/chamber regions 127-129. In this embodiment, the
central stencil layer 123 has a greater height than the other
layers, and the layers 122 and 124 are flexible or deformable
membranes. Fluid flow through the central channel segment 128 is
affected by both the upper chamber region 127 and the lower chamber
region 129. FIG. 3B shows the central channel segment 128 being
partially blocked following a pressure increase within the upper
chamber 127, causing deflection of the upper membrane 122 toward
and into the central channel 128. FIG. 3C shows the channel segment
128 being substantially (almost completely) blocked following
pressure increases in both the upper and lower chamber 127, 129,
which cause both membranes 122, 124 to deform toward and into the
central channel 128. FIG. 3D shows another operating state wherein
the channel segment 128 is partially blocked following a pressure
increase in the lower chamber region 129. In FIG. 3E, the central
channel segment 128 is enlarged in response to a reduced pressure
in both the upper and lower chambers 127, 129.
[0061] In the operation of a device of the invention, a
differential pressure can be generated between a first and a second
channel segment either by increasing the pressure in one channel
segment, or through a relative decrease in pressure in one channel
segment. The pressure of a fluid (encompassing both liquids and
gases) can be increased by a pump such as, for example, a syringe
or other mechanically operated pump. Reduced pressure can be
achieved in the channel segment by applying a vacuum to a channel
segment, for example using a vacuum pump. Where a channel segment
is pressurized to greater than atmospheric pressure and a pressure
reduction is desired, then the pressure can be reduced by venting
the channel segment to the atmosphere or to a lower-pressure
reservoir. Pressure can also be controlled by changing the
temperature within one channel segment of the device. In such an
embodiment, it is preferred that the fluid within the channel
segment undergoes a large volume change with changing temperature.
Preferably, in such an embodiment the fluid is a gas. The pressure
can be increased by raising the temperature of the gas within the
channel segment and can be decreased by lowering the temperature
within the channel segment. The pressure within a channel segment
also can be changed by processes such as vaporization or
electrolysis (a process in which an electric current is used to
break a liquid within a channel segment into gaseous components).
For example, water may be electrolyzed into hydrogen gas and oxygen
gas.
[0062] Microfluidic membrane valves may be actuated with means
other than pressure. For example, a membrane can be moved within a
device manually or with a mechanical actuator. Mechanical actuators
include, for example, a piston, a solenoid, and a lever. The
flexible membrane also can be coupled to a material that alters
shape in response to a stimulus, for example, heat or an electric
current. Titanium-Nickel composites are known that undergo large
conformational changes in response to changes in temperature. Such
a composite can be incorporated into the deformable membrane. When
heated, as by passing an electric current through the composite,
the composite will change shape and deflect the deformable
membrane. The membrane also can be constructed of a magnetic
material, or provided with a magnetic coating. As will be discussed
further hereinafter, deformation of such a membrane can be achieved
using an external magnet, including an electromagnet or an electric
field generator.
[0063] Microfluidic membrane valves may be combined into more
complex devices. The embodiments shown in FIGS. 3A-3E and others
form the basics of microfluidic logic elements. For example, the
embodiment shown forms a microfluidic AND/OR element. Consider
measuring the flow in the central channel 128 at a constant
backpressure. In FIG. 3A, the flow through the channel 128 may be
considered to be 1 unit, in FIG. 3B about {fraction (1/2)} of one
unit, in FIG. 3C about 0 units, in FIG. 3D about 1/2 of one unit,
and in FIG. 3E about 2 units. It follows that:
1 IF P127 = P128 AND P128 = P129 THEN Flow = 1 IF P127 = P128 AND
P128 < P129 OR IF P129 = P128 AND P128 < P127 THEN Flow =<
1 IF P127 > P128 AND P129 > P128 THEN Flow =<< 1 IF
P127 < P128 AND P129 < P128 THEN Flow => 1
[0064] In another preferred embodiment, the flow control elements
shown in FIGS. 3A-3E can be combined in a network in order to make
a two dimensional fluid control system. Referring to FIG. 5A, a
network of channels 150 are defined in the center layer of a three
dimensional device. The channel network has multiple inlet ports
151 and outlet ports 152. Any given inlet port is in fluidic
connection with all of the outlet ports in the unaltered layer.
When assembled in a flow control device 180, the channels 150
depicted in FIG. 5A will be disposed between control channels and
flexible membranes, such as the channel segment 128 shown in FIGS.
3A-3E.
[0065] Two control layers are also made within the device, one
disposed above and one disposed below the channel network 150.
Referring to FIG. 5B, the upper control layer of the
three-dimensional device includes four vertical control channels
160-163, and the lower control layer of the device has four
horizontal control channels 156-159. These control channels 160-163
and 156-159 overlap in specific regions 155. The cross-section of
each of these overlap regions 155 are the same as those shown in
FIGS. 3A-3E. Thus, control channels 160-163 are represented in
cross section by the channel segment 127 in FIGS. 3A-3E and the
control channels 156-159 are represented in cross section by the
channel segment 129 of FIGS. 3A-3E.
[0066] Two flexible membranes, one disposed on either side of the
channel network 150, separate the channel network 150 from the
upper and lower control layers. These membranes may be homogeneous
membrane layers, or they may be heterogeneous layers to permit the
valving or flow control characteristics at any particular region to
be "tuned." Examples of heterogeneous membrane layers are provided
in FIGS. 5C-5D. In FIG. 5C, a first heterogeneous membrane layer
175 is composed of four membrane regions 175A-175D, any of which
may be formed of different materials to provide desired response
characteristics for each quadrant of four nodes or intersections of
control channels. In FIG. 5D, a second heterogeneous membrane layer
176 is composed of sixteen membrane regions 176A-176P to permit the
response characteristics for each individual overlap region 155 to
be separately tuned if desired.
[0067] Referring to FIG. 5E, the various layers of the flow control
device 180 may be assembled in the following order: a lower
substrate, a lower control channel layer, a lower flexible membrane
layer, a central channel network layer, an upper flexible membrane
layer, an upper control channel layer, and finally an upper
substrate or cover. In use, any given inlet port 151 can be
connected to any given outlet port 152 by simply controlling the
pressures of the control channels 160-163 and 156-159. This may be
accomplished with a fluid control system 320 such as illustrated in
FIG. 5F. There, the pressure to individual control channels 156-159
and 160-163 is supplied by two pressure sources 302, 304 and
regulated by control valves 326A-326D and 328A-328D, which are
preferably three-way valves or the equivalent to permit excess air
to be released if necessary. Each valve 326A-326D and 328A-D is
controlled by a controller 313. The controller 313 is preferably
electronic, and more preferably microprocessor-based. The
controller 313 may be programmed to execute complex, sequential or
repetitive fluid functions on the device 180. One or more sensors
329 may be in sensory communication with the microfluidic flow
control device 180 and coupled to the controller 313 to provide
feedback and/or sensory data to be stored in or otherwise used by
the controller. An input device 331 and display 332 may be coupled
to the controller 313 to aid with programming and processing
sensory data, among other functions.
[0068] An example showing operation of the microfluidic device 180
is shown in FIG. 5E. In this example, a pressure of 20 psi (138
kPa) is applied to control channel segment 157, negative 10 psi (69
kPa) is applied to control channel segment 160, and positive 10 psi
(69 kPa) is applied to control channel segment 159. All of the
other control channels are left at atmospheric pressure. All of the
fluid channels under control channel segment 157 are blocked,
because 10 psi (69 kPa) is sufficient to substantially block the
channels. The valve regions of interest are 170, 171, and 172. At
point 170, the upper control chamber has 20 psi (69 kPa), and the
bottom control chamber has -10 psi (69 kPa) for a net of +10 psi
(69 kPa), which is sufficient to locally block the fluid channel in
network 150. At point 171, the bottom has negative 10 psi and the
channel segment is opened more. At point 172, the +10 psi (69 kPa)
applied to the top control channel equals the -10 psi (69 kPa)
applied to the bottom control channel, and the central channel
segment remains open. For the rest of the channels along the
control channel 159, all are closed because they experience 10 psi
(69 kPa). Thus, the fluid supplied to the central channel layer 150
through the input ports 151 can only take the pathway shown by the
arrow. Alternatively, any outlet port 152 can be reached by varying
the pressure combinations to the control channels 156-159 and
160-163.
[0069] In a further embodiment, a flow control device can have more
than one channel segment on a given layer at a regulatory region.
As shown in FIGS. 7A-7B, a microfluidic device 699 includes two
channel segments 706 and 707 defined in layer 703 and separated by
a deformable membrane 702 from a channel segment 705 defined in an
upper layer 701. The deformable membrane 701 is not adhered a
seating region 703A defined in the layer 703. When the pressure in
the channel segment 705 is high relative to both channels 706 and
707, then fluid communication between the channels 706 and 707
within the regulatory region is prevented by the membrane 702
pressed into contact with the seating region 703A, such as shown in
FIG. 7A. If the relative pressures in both channels 706 and 707 are
higher than that in the channel 705, such as shown in FIG. 7B, then
the membrane 702 will deform toward and into the channel segment
705, thus allowing fluidic passage between the channels 706 and
707. Factors affecting whether an increased pressure in channel
segments 706 or 707 is sufficient to open a flow path between the
channels indude the size of the seating region, the thickness and
composition of the flexible membrane 702, and the size of the
regulatory region (which affects the size of the membrane subject
to deformation).
[0070] Flow Control Devices with Feedback
[0071] In further embodiments, pressure-sensitive regions may be
integrated into a microfluidic device to provide internal feedback,
such that a change in pressure or flow rate within one region of a
channel segment will affect another region.
[0072] In a preferred embodiment, a feedback loop is used to create
a pressure regulation device. A microfluidic device is constructed
where a first channel segment located in one layer of a
three-dimensional device is in fluid communication with a second
channel segment in another layer of the device. For example, the
two channels in distinct layers may be connected through a via or
through-hole between layers. In an upper layer, one channel segment
is positioned so that it passes back over the other channel segment
in a lower layer. This upper section can pass over the lower region
one or more times and can pass over the channel segment in parallel
along its axis or cross the channel segment at an angle. A
deformable membrane separates the two channel segments at a
regulatory region. A pressure increase in the upstream part of the
channel segment will cause the first channel segment to expand,
thus compressing the overlapping downstream part of the channel
segment. This will deform the membrane towards the second channel
segment, altering the shape or geometry of the second channel
segment. The flow through the second segment also can decrease, and
will vary depending on the design of the regulatory region and with
the pressure applied. The membrane can provide a partial blockage
or a substantially complete blockage to fluid flow through one
channel segment. A subsequent decrease in the pressure within the
channel segment will result in said channel segment attaining its
previously unrestricted or "relaxed" neutral state.
[0073] A pressure-activated valve can regulate flow between two
channel segments in a single microfluidic channel because of the
pressure-drop that occurs "downstream" in microfluidic channels.
The pressure within a microfluidic channel decreases with distance
from the inlet port. At low input pressures, there is a minimal
pressure drop in a long channel segment. As the input pressure
increases, it becomes more difficult for the internal pressures to
equalize, and the pressure differential from one end of a channel
segment to the other is much larger. The higher the operating
pressure of the microfluidic device, the greater the pressure
differential generated over the length of a channel. Thus, by
designing different microfluidic systems having valves separated by
different lengths of channel between one side of the pressure
membrane and the other, different shut-off pressures can be
designed or "programmed" into the device. For example, in FIGS.
6A-6B (which is discussed in further detail below), a relatively
long channel segment connects the one side of the shut-off valve
membrane and the other; a long channel segment length is preferably
provided to create the pressure differential.
[0074] A microfluidic device with a built in pressure regulation
system is shown in FIGS. 4A-4B. Referring to FIG. 4A, a
microfluidic device 130 was constructed using a sandwiched stencil
fabrication method from five layers 131-135. The first layer 131
defines one inlet port 136 and two outlet ports 137, 138. The
second layer 132 defines two vias 140 and a channel segment 139
having a nominal width of 40 mils (1000 microns). The third layer
133 defines a central via 141 and two lateral vias 142. The fourth
layer 134 defines a channel 143 also having a nominal width of 40
mils (1000 microns). All of the vias are 70 mils in diameter. The
layers 131-134 stencil layers are all constructed from 3 mil (75
microns) thickness single-sided tape comprising a polypropylene
carrier with a water-based adhesive. The bottom stencil 100 is a
0.25 inch (6.3 mm) thick block of acrylic.
[0075] In use, fluid is injected at inlet port 136 at a low
backpressure. The fluid passes through channel segment 139 until it
reaches junction point 144. The fluid then splits evenly down the
two parts of channel segment 143 until it reaches the outlet ports
137 and 138. As fluid continues to flow, the fluid splits evenly at
the junction point 144 and is divided evenly. When increased
pressure was applied at the entry port 136, the pressure within the
channel segment increased, as did the flow rate. In the region 145
where channels 139 and 143 overlap, the pressure in the upper
channel segment 139 pushes on the polymeric membrane 133 that
separates the two channels. The polymer material 133 is locally
deformed and partially blocks the lower channel segment 143, thus
partially restricting the flow in that channel segment.
[0076] In a preferred embodiment directed to this example, the size
of the exit channels are adjusted such that the flow out of the
device 130 remains constant no matter what backpressure is applied.
This device 130 may be used in various applications, including but
not limited to constant delivery of materials such as in drug
delivery applications. In a preferred embodiment, inlet port 136 is
connected to a pressurized container of fluid (not shown) that
contains a drug of interest. The outlet ports 137, 138 are
connected to a delivery mechanism to a body. When the pressurized
container is full, the backpressure is high and the outlet 137 is
closed and 138 is open. Although the pressure remains high, the
resistance in the channels is even higher since there is only one
outlet. As the pressurized body loses fluid, the pressure decreases
which permits the exit port 137 to slowly open. As the pressure
drops, the resistance in the channels decreases since two channels
are now open. A more complicated structure with many feedback loops
can be constructed so that approximately constant flow can be
maintained over a large range of input pressures.
[0077] In a further embodiment, a microfluidic device was
constructed to regulate flow rate over a large range of input
pressures. Referring to FIGS. 6A-6B, a microfluidic flow regulation
device 199 was constructed using a stencil fabrication method from
five layers 200-204. Starting from the bottom, the first layer 204
defined one inlet port 209 and two outlet ports 210, 211. The
second layer 203 defined a via 214 and a channel 206 terminating at
a chamber 207. The third layer 202 defined two vias 208, 208A. The
fourth layer 201 defined a channel 205 and connected chamber 215.
The fifth layer 200 served as a cover for the fourth layer 201. The
assembled device is shown in FIG. 6B. The overlap region 212 is
shown in cross section in FIGS. 6C-6D with the valve in open and
closed positions, respectively. In use, fluid is injected into the
inlet port 209. The fluid travels through the vias 214, 208,
through channel segment 205, down through the via 208A and the
channel 206 and is split towards the two exit ports 210 and 211.
When the inlet pressure is relatively low, the flexible membrane
202 is not substantially deformed (see FIG. 6C) and the fluid
passes evenly out of the two exit ports 210, 211. As the pressure
at the inlet is increased, the pressure in the channel 205 and
chamber 215 increases, thus deforming the membrane 202 (see FIG.
6D) and partially blocking the outlet port 210.
[0078] Two sets of experiments were performed with this device 199.
In the first experiment, the pressure versus flow characteristic of
the two exit ports 210 and 211 were measured independently. One of
the exit ports was completely blocked, and the pressure at the
inlet 209 versus flow at the outlet was measures. Referring to FIG.
6E, for exit port 211 (unregulated), the flow rate increases as the
pressure increases, as would be expected. However, for the
(regulated) exit port 210, as the pressure increases above 3 psi
(21 mPa), the membrane 202 is deformed, resulting in a constricted
channel segment. The device 199 acts as a flow regulator. As the
pressure increases further, the flow remains constant since flow is
proportional to pressure and channel segment dimension. As the
pressure increases, the channel segment dimension decreases,
resulting in substantially constant flow rates.
[0079] The same experiment was repeated when both channels were
measured simultaneously. The results of this experiment are
provided in FIG. 6F. Again, the flow is regulated, but in this
case, the flow is regulated to an even lower flow rate.
[0080] A structure substantially similar to that illustrated in
FIGS. 6C-6D is provided in FIGS. 12A-12B, with the primary
difference being the addition of outlet channels 222 defined by
stencil layer 220 and a substrate 221 to continue flow within the
device 197.
[0081] Magnetically actuated flow control devices
[0082] In another embodiment, a flow control device such as a valve
is magnetically actuated. Generally, magnetic actuation requires a
field generator and a magnetic (i.e,, paramagnetic or
ferromagnetic) element. The magnetic element moves in response to
application of a magnetic field, with the direction of motion of
the magnetic element depending on the direction of the applied
magnetic field. Opening or closing force of a magnetically actuated
valve may be adjusted by varying the magnitude of the applied
magnetic field, or selecting a magnetic element with appropriate
response characteristics (e.g., magnetization). For example, if
strong magnetization is desirable, then magnetic elements formed
from rare earth magnetic materials may be used.
[0083] Preferably, at least one magnetic element is integrated into
a microfluidic flow control device and used in conjunction with a
deformable membrane. In a preferred embodiment, a deformable
membrane includes one or more discrete magnetic elements. A
discrete magnetic element may be attached to a deformable membrane
using various means including adhesives and mechanical retention.
For example, FIG. 8A illustrates a magnetic element 400 affixed to
a deformable membrane 401 using an adhesive. In a more preferred
embodiment shown in FIG. 8B, a discrete magnetic element 402 is
sandwiched between multiple deformable membrane layers 403, 404.
Contact between the layers 403, 404 and the magnetic element 402
may be maintained with an adhesive, such as if one of the layers
403 is formed of a self-adhesive tape material. Further preferably,
as shown in FIG. 8C, a central membrane layer 407 may be a stencil
layer defining an aperture into which a magnetic element 405 may be
inserted. Multiple membrane layers 406-408 may be laminated
together using conventional bonding methods such as, for example,
adhesive or thermal bonding. In a preferred embodiment, at least
one membrane layer containing the discrete magnetic element
comprises a self-adhesive tape material. Adhesiveless films of
deformable materials such as latex, polypropylene, polyethylene,
and polytetrafluoroethylene are readily available in thicknesses of
approximately 0.5 mil (13 microns) or less. If supplied as
self-adhesive tape, such materials are readily available with a
total (carrier plus adhesive) thickness between approximately 1.5
and 2.0 mils (38 to 50 microns). An embodiment such as shown in
FIG. 8B may thus be provided with a combined membrane thickness of
approximately 2.0 to 2.5 mils (50 to 63 microns). In an embodiment
such as shown in FIG. 8C, the central layer 407 may be a stencil
layer formed of contact adhesive, so as to form a laminated
membrane of approximately the same total thickness as before
(approximately 2.0 to 2.5 mils, or 50 to 63 microns).
[0084] A discrete magnetic element to be integrated with a membrane
layer may be provided in any size or shape sufficient to promote
the desired flow control characteristics. If the flow control
device utilizes a valve seat of a particular geometry, then the
desired shape and size of the magnetic element is preferably
selected to interface with the valve seat geometry. Particular
shapes of magnetic elements that may be used include cylindrical,
spherical, or annular shapes. A valve seat may include an aperture
that may be selectively sealed to control fluid flow. Preferably,
the membrane may be deformed by magnetic force to seal the
aperture, thus preventing fluid flow. Alternatively, an annular
magnetic element may be disposed adjacent to an aperture defined in
a membrane, so that under certain conditions fluid is permitted to
flow through both the membrane aperture and the annular magnetic
element. This fluid flow path may be selectively blocked or
re-established through application of a magnetic field that deforms
the membrane against a valve seating surface.
[0085] As an alternative to using one or more discrete magnetic
elements, a flexible membrane comprising a diffuse magnetic layer
may be provided. If a diffuse magnetic layer is used, then it is
preferably coupled to a deformable membrane selected for desirable
material properties such as chemical compatibility or sealing
characteristics.
[0086] The magnetic field generator preferably comprises a coil of
current-carrying wire, preferably insulated wire. Current may
selectively applied to the coil, such as by using an external
current source, to generate a magnetic field. The strength of the
magnetic field may be adjusted by varying the magnitude of the
current and the number of turns of wire. The direction of the
resulting magnetic field is parallel to the central axis of the
coil. In a more preferred embodiment, a field-concentrating
element, such as a ferromagnetic core, is provided along the
central axis of the coil. A magnetic field generator 425 having a
field-concentrating element 427 and a coil of insulated wire 426 is
shown in FIGS. 9A-9B. The field-concentrating element 427 is
preferably substantially cylindrical in shape, and if a highly
focused field is desired then the cylinder should be of a small
diameter. The current-carrying wire 426 may be directly wrapped
around the field-concentrating element 427.
[0087] As further shown in FIGS. 9A-9B, a magnetically actuated
membrane valve is operated by selectively applying current to the
coil 426. To deform the membrane 411 (formed from laminated layers
411A-411C and magnetic element 417) in one direction, current in
one direction is applied to the coil 426. To reverse the travel of
the membrane 411, current is applied in the opposite direction.
FIG. 9A shows the membrane 411 in a relaxed position, with the
field generator 425 substantially centered above the magnetic
element 417, which in turn is substantially centered over an
aperture 420 permitting fluid communication between a first channel
segment 418 and a second channel segment 419 within a microfluidic
flow control device 410. The flow control device 410 is formed from
a three-layer composite membrane 411 and four other device layers
413-416. FIG. 9B shows the membrane 411 in a deformed position and
contacting the seating layer 414 adjacent to the aperture 420 to
prevent fluid flow between the first channel segment 418 and the
second channel segment 419.
[0088] In a preferred embodiment, multiple magnetically actuated
flow control valves may be integrated into a single microfluidic
device. Referring to FIG. 10, a microfluidic flow control device
430 includes at least one flexible membrane and multiple discrete
magnetic elements 431. Preferably, the device 430 may be used to
manipulate fluid between multiple fluidic inlet ports 432 and
multiple outlet ports 433. A magnetic field generator array 435
having multiple coils and field concentrating elements 436 may be
positioned in relatively close proximity to the microfluidic flow
control device 430 to manipulate fluid within the device 430.
However, the field generator array 435 preferably does not contact
the microfluidic device 430. Preferably, one coil and field
focusing element 436 is provided and paired with each magnetic
element 431. One advantage of using field focusing elements in such
a device is to minimize unwanted interference between unpaired
coils and magnetic elements. High density arrays of field
generators may thus be used to provide precise control over fluid
flowing in a small area. Complex operation of a fluidic system can
thus be provided without requiring any external to ever physically
contact the device 430. For example, utility similar to that
described in connection with FIGS. 5A-5F may be provided.
[0089] Various elements of a magnetically actuated microfluidic
flow control system 450 and their interconnections are illustrated
schematically in FIG. 11. Preferably, a controller 442 is provided
to selectively apply currents to the various field generator coils
436, such as may be contained in a field generator array 435. The
controller 442 is preferably electronic, and more preferably is
microprocessor-based, and receives power from a power source 444.
In a preferred embodiment, the controller 442 is programmable to
permit execution of complex, repetitive and/or sequential functions
with minimal user interaction. Preferably, one or more sensors 440
are included in sensory communication with the microfluidic device
430 to provide feedback and/or useful data to the controller 442.
Suitable sensors may include, for example, pressure sensors, flow
sensors, optical sensors, and displacement sensors. If the provided
sensors are capable of inferring fluid flow, then the system may be
used to provide flow regulation utility. More specifically,
feedback from a flow sensor may be provided to the controller 442,
which in turn may provide an analog signal to one or more field
generators to regulate flow. Alternatively, pressure regulation
utility may be provided in a similar fashion. An input device 446
and display 448 are preferably coupled to the controller 442 to aid
in programming and/or analyzing data generated by the system
450.
[0090] The particular devices and construction methods illustrated
and described herein are provided by way of example only, and are
not intended to limit the scope of the invention. The scope of the
invention should be restricted only in accordance with the appended
claims and their equivalents.
* * * * *