U.S. patent application number 11/119480 was filed with the patent office on 2006-11-02 for valve and pump for microfluidic systems and methods for fabrication.
This patent application is currently assigned to General Electric Company. Invention is credited to Ernest Wayne Balch, Jeffrey Bernard Fortin, Thomas Bert Gorczyca, Andrew Michael Leach, Radislav Alexandrovich Potyrailo.
Application Number | 20060245933 11/119480 |
Document ID | / |
Family ID | 37234625 |
Filed Date | 2006-11-02 |
United States Patent
Application |
20060245933 |
Kind Code |
A1 |
Balch; Ernest Wayne ; et
al. |
November 2, 2006 |
Valve and pump for microfluidic systems and methods for
fabrication
Abstract
A microfluidic system and method for its fabrication is
disclosed comprising an interposed intermediate layer covering the
channel-containing layers, said intermediate layers comprising an
integral valve made from the intermediate layer material. A
microfluidic system and method is also disclosed for actively
pumping a fluid through an integrated layered device incorporating
the above-mentioned channels, valves in communication with a
chamber, the volume of which can be predictably controlled by
interaction between a magnetizable assembly placed on pre-selected
sides of the chamber.
Inventors: |
Balch; Ernest Wayne;
(Ballston Spa, NY) ; Gorczyca; Thomas Bert;
(Schenectady, NY) ; Potyrailo; Radislav
Alexandrovich; (Niskayuna, NY) ; Fortin; Jeffrey
Bernard; (Niskayuna, NY) ; Leach; Andrew Michael;
(Clifton Park, NY) |
Correspondence
Address: |
GENERAL ELECTRIC COMPANY;GLOBAL RESEARCH
PATENT DOCKET RM. BLDG. K1-4A59
NISKAYUNA
NY
12309
US
|
Assignee: |
General Electric Company
|
Family ID: |
37234625 |
Appl. No.: |
11/119480 |
Filed: |
May 2, 2005 |
Current U.S.
Class: |
417/182 |
Current CPC
Class: |
F16K 2099/0084 20130101;
F16K 99/0034 20130101; F16K 2099/0078 20130101; F16K 99/0001
20130101; F16K 99/0046 20130101; B01L 2300/0887 20130101; B01L
3/502707 20130101; B01L 2200/12 20130101; B01L 3/502738 20130101;
F16K 99/0057 20130101; F16K 2099/0074 20130101; B01L 2400/0638
20130101; F16K 2099/0076 20130101; F16K 2099/008 20130101 |
Class at
Publication: |
417/182 |
International
Class: |
F04F 5/48 20060101
F04F005/48 |
Claims
1. A microfluidic device comprising: a first layer comprising a
channel, said first layer made from a first material; and a second
layer made from a second material, said second layer in intimate
contact with the first layer, said second layer comprising an
integral valve made from the second material.
2. The microfluidic device of claim 1, further comprising a metal
release layer deposited onto the first layer.
3. The microfluidic device of claim 2, wherein the metal release
layer comprises gold.
4. The microfluidic device of claim 1, wherein the first material
comprises silicon.
5. The microfluidic device of claim 1, wherein the second material
is selected from the group consisting of polyimide-,
polyscarbonate-, polysulfone-, polyether ether ketone-,
polyvinylidene fluoride-containing compounds, and mixtures
thereof.
6. The microfluidic device of claim 1, wherein the second material
comprises Kapton.RTM..
7. The microfluidic device of claim 1, wherein the integral valve
seals a channel present in the microfluidic device when a first
channel flow pressure exceeds a second channel flow pressure.
8. The microfluidic device of claim 1, wherein the integral valve
is adapted to allow flow from a secondary channel into a first
channel when a second channel flow pressure exceeds a primary
channel flow pressure.
9. The microfluidic device of claim 1, further comprising a
plurality of valves.
10. A microfluidic device comprising: a multilayered structure,
said structure comprising a first layer made from a first layer
material and having at least one channel, and a second layer made
from a second layer material, said second layer in intimate contact
with the first layer, said second layer comprising an integral
valve made from the second layer material, and said integral valve
aligned and dimensioned to cover a channel.
11. The microfluidic device of claim 10, wherein the second layer
is made from a material selected from the group consisting of
polyimide-, polyscarbonate-, polysulfone-, polyether ether ketone-,
polyvinylidene fluoride-containing compounds, and mixtures
thereof.
12. The microfluidic device of claim 10, wherein the second layer
material comprises Kapton.RTM..
13. A method for analyzing an analyte comprising the steps of:
providing a microfluidic device comprising a multilayered
structure, said structure comprising a first layer made from a
first layer material having at least one channel, and a second
layer made from a second layer material, said second layer in
intimate contact with the first layer, said second layer comprising
an integral valve made from the second layer material, said valve
aligned and dimensioned to cover a channel; providing an amount of
analyte; introducing the amount of analyte to the microfluidic
device; and analyzing the analyte.
14. A method for analyzing an analyte comprising: providing a
microfluidic device comprising a first channel-containing layer and
a second channel-containing layer with an intermediate layer
interposed between, and in intimate contact with the first and
second channel-containing layers, said intermediate layer
comprising an integral valve aligned and dimensioned to cover at
least one channel; providing an amount of analyte; introducing the
amount of analyte to the microfluidic device; and analyzing the
analyte.
15. A method for making a microfluidic device, comprising:
providing a substrate made from a substrate material; providing a
channel-containing layer; positioning the channel-containing layer
in intimate contact with the substrate; providing a cover layer
made from a cover material; providing an intermediate layer;
machining the intermediate material to create a flexible structure,
said flexible structure dimensioned to cover a channel in the
channel-containing layer; and positioning the intermediate layer in
intimate contact between the channel-containing layer and the cover
layer.
16. A microfluidic device comprising: a structure having multiple
layers, said structure comprising a first channel in communication
with a first valve, said first valve having an outlet in
communication with a chamber, said chamber having an outlet in
communication with a second valve, said second valve in
communication with a second channel.
17. The microfluidic device of claim 16, wherein the first and
second channels each have an initial volume, wherein said initial
volume can be predictably altered.
18. The microfluidic device of claim 16, further comprising a
magnet positioned proximate to a layer or layers positioned over a
first side of the chamber.
19. The microfluidic device of claim 18, further comprising an
electrical coil structure positioned proximate to at least one
layer positioned over a second side of the chamber.
20. The microfluidic device of claim 19, wherein the coil is
activated, and such activation will facilitate an increase or
decrease in the initial chamber volume.
21. The microfluidic device of claim 20, wherein the increase or
decrease in initial chamber volume is predictably regulated to
effect a pumping action in the chamber.
Description
BACKGROUND
[0001] The present invention is directed generally to the field of
microfluidic devices. More particularly the present invention is
directed to novel valving components for microfluidic devices where
such valve components are fabricated integrally on the device
substrate.
[0002] In microfluidic systems, development of on-chip propulsion
and valving components is important, for example, to reduce or
eliminate the sample dead volumes and, thus, to improve the
analytical performance of a microfluidic system. Use of
microfluidic chip valves is known. See U.S. Pat. Nos. 6,581,899;
6,575,188; 6,561,224; 6,527,003; 6,523,559; 6,448,090; 6,431,212;
6,406,605; 6,395,232; 6,382,254; 6,318,970; 6,068,751; 5,932,799,
all of which are incorporated by reference herein as if made part
of the present specification. However, the need exists in improving
parameters of existing reported valves for microfluidic systems. In
particular, existing valves suffer from being too large, too
expensive, having poor respond time, or not being sufficiently
robust. In addition, there is a need to integrate such valves with
a diaphram chamber, to achieve the positive flow or pumping of the
fluid in a microfluidic device Use of magnet for movement in a
laminated structure is known. See U.S. Pat. No. 5,472,539, which is
incorporated by reference herein. However, the integration of
magnet activation for a pump chamber incorporating valves in a
laminated microfluidic device is not known.
SUMMARY
[0003] It is highly desirable to develop a valve that is
intrinsically located on a microfluidic chip and meets the
requirements of small size and low fabrication cost. Embodiments of
the invention address the limitations of known valves for
microfluidic systems and are directed to a new type of valve for
incorporation in microfluidic systems.
[0004] Embodiments of the invention are further directed to a
valve, preferably a microfluidic valve, fabricated on the same
substrate as the microfluidic channels in a microfluidic
device.
[0005] In addition, embodiments of the invention are directed to a
microfluidic device having a first layer made from a first material
having a channel, and a second layer made from a second layer
material. The second layer is in intimate contact with the first
layer, and the second layer comprises an integral valve made from
the same material as the second layer material.
[0006] Still further, embodiments of the invention are directed to
a microfluidic device having a multilayered structure with a first
layer made from a first layer material and having at least one
channel, and a second layer made from a second layer material, with
second layer in intimate contact with the first layer. The second
layer comprises an integral valve made from the second layer
material, with the valve aligned and dimensioned to cover a
channel.
[0007] Yet, still further, embodiments of the invention are
directed to a method for analyzing an analyte by providing a
microfluidic device comprising a multilayered structure. The
structure includes a first layer made from a first layer material
and having at least one channel, and a second layer made from a
second layer material, with the second layer in intimate contact
with the first layer. The second layer comprises an integral valve
made from the second layer material, and the valve aligned and
dimensioned to cover a channel. An amount of analyte is then
provided and introduced to the microfluidic device, and is then
analyzed.
[0008] Embodiments of the invention are also directed to a method
for analyzing an analyte including the steps of providing a
microfluidic device having a first channel-containing layer and a
second channel-containing layer with an intermediate layer
interposed between, and in intimate contact with the first and
second channel-containing layers. The intermediate layer comprises
an integral valve aligned and dimensioned to cover at least one
channel. An amount of analyte is provided and introduced to the
microfluidic device, and is then analyzed.
[0009] According to another embodiments, there is provided a
structure for actively pumping a fluid through an integrated,
layered device including above-mentioned channels and valves. In
such a preferred structure, the device has a chamber acting as a
diaphram, with the volume of the chamber controlled by the
interaction between a magnet placed on one side of the chamber and
an electrical coil place on another side of the chamber. Activation
of the coil to attract the magnet compresses the chamber, pushing
fluid out through one check valve, while coil activation to repel
the magnet expands the chamber, bringing fluid into it through
another check valve. Such a structure can be used to control the
amount and type of analyte provided to other areas of the
microfluidic device.
[0010] These and other advantages and features will be more readily
understood from the following detailed description of preferred
embodiments of the invention that is provided in connection with
the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] FIGS. 1A and 1B are schematic representations of one
embodiment constructed in accordance with the invention showing an
integrated valve of the device in operation as pressure
differentials occur within channels.
[0012] FIGS. 2A and 2B are schematic representations of another
embodiment constructed in accordance with the invention showing an
integrated valve of the device in operation.
[0013] FIG. 3 is a cross-sectional side view of another embodiment
of the microfluidic valve device of the present invention.
[0014] FIGS. 4A and 4B are overhead and cross-sectional side views,
respectively, of another embodiment of the microfluidic valve
device of the invention showing the glass substrate and first
channel layer.
[0015] FIGS. 5A and 5B are overhead and cross-sectional side views,
respectively, of the microfluidic valve device of FIGS. 4A and 4B
showing the addition of connecting via layer on the first channel
layer.
[0016] FIGS. 6A and 6B are overhead and cross-sectional side views,
respectively, of the microfluidic valve device of FIGS. 5A and 5B
showing the addition of gold release and valve layers on the
connecting via layer.
[0017] FIGS. 7A and 7B are overhead and cross-sectional side views,
respectively, of the microfluidic valve device of FIGS. 6A and 6B
showing the second channel layer on the via layer.
[0018] FIG. 8A is an overhead view of a device constructed in
accordance with embodiments of the invention, the device having
multiple check valves in place to form a microfluidic circuit.
[0019] FIG. 8B is a schematic representation of the device shown in
FIG. 6A.
[0020] FIG. 9 is a cross-sectional schematic diagram of a
microfluidic device constructed in accordance with embodiments of
the invention and incorporating a diaphragm chamber activated by
interaction between a magnet placed on top of the uppermost layer,
and a coil patterned on the underlying substrate. Arrows on the
schematic show the direction of fluidic flow during operation of
the diaphragm chamber.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0021] Embodiments of the invention are directed to a valve
incorporated in microfluidic systems with one or more of the
following features. The microfluidic valve is located integrally
within the microfluidic system and therefore is desirably
dimensioned to selectively and predictably seal channels or
otherwise direct flow within a channel of a microfluidic device.
The valve is preferably made from the same material as the
microfluidic device substrate and therefore has a desirably low
cost and low fabrication processing cost.
[0022] Operation of the valve is depicted in FIGS. 1A-1B and 2A-2B.
Upon applying pressure P.sub.0 to a valve where P.sub.0 is less
than the critical opening pressure P.sub.C created by the main flow
(with arrow indicating flow direction), the valve remains closed
and only the main flow is passing through the microfluidic channel
(see FIG. 1A). Upon applying pressure P.sub.1 to the valve where
P.sub.1>P.sub.C, the valve is open and the second flow is
passing into the microfluidic channel (see FIG. 1B).
[0023] Alternatively, the valve can be used as a passive one-way
flow controller. For example, as shown in FIGS. 2A and 2B, when the
pressure in a Channel 1 is greater than the pressure in the second
Channel 2, the pressure difference will force the valve to open and
allow flow from the Channel 1 toward the Channel 2. However, when
the pressure in the Channel 2 is greater than the pressure in the
Channel 1, the position of the valve will be dictated by the valve
seat, resulting in a closure of the valve and no further liquid
flow, in this case, from Channel 1 into Channel 2 or from Channel 2
into Channel 1.
[0024] FIG. 3 shows a cross-sectional side view of a microfluidic
device having a check valve 9. A first layer 10 made from a first
layer material, is in contact with, and preferably laminated to, a
second layer 12 made from a second layer material. A substrate 24,
such as a silicon--(Si), glass-, or plastic-based substrate, having
a channel 20, is provided and brought into contact with a third
layer 22 made from a third layer material. Preferably the substrate
24 is adhered to the third layer 22. The third layer 22 also has a
channel 18. At least a portion of the channel 20 of the glass
substrate 24 overlaps at least a portion of the channel 18 of the
third layer 22. A metal, preferably gold, or other non-stick layer
16 of a predetermined size is positioned to cover the channel 18
and preferably extends beyond the channel 18. The layers are
preferably adhered together. A laser cut 14 made in the second
layer 12, thereby forming a check valve, or flap-like structure 9.
According to the present invention, the laser cut is typically made
in a "U" shape to allow formation of a flap thus making the check
valve 9.
[0025] As shown in FIG. 3, the solid arrow indicate the fluid flow
direction. The check valve 9 opens in response to vacuum. The small
area opening 21 on the input side of the device may be designed to
inhibit pressure to push the check valve open. The check valve 9
should, however, preferably allow a slight vacuum on the output
side 23 of the device to open the check valve 9. Thus, according to
this embodiment, the presence of the check valve 9 insures
unidirectional movement of the fluid flowing through the channel
20.
[0026] FIGS. 4A and 4B respectively show a top view and a
cross-sectional side view of a partial construction of a device
made according to one embodiment of the invention. As shown, a
glass substrate 26 is in contact with a layer 28 having a first
channel 29. Preferably, the first channel 29 is laser
micro-machined into layer 28. Fluid can access channel 29 through
substrate 26 from channel 17.
[0027] FIGS. 5A and 5B respectively show a top view and
cross-sectional side view of the construction of FIGS. 4A and 4B.
An additional layer 22 is in contact with layer 28 with opening via
30 machined through layer 22.
[0028] FIGS. 6A and 6B show the progressive construction shown in
FIGS. 5A and 5B with an additional metal release layer 16 placed
over via 30 and thus, over a portion of layer 22. A valve layer 12
is then placed over the metal release layer 16. A "U"-shaped cut 14
is made through valve layer 12 to the metal release layer 16 as
shown in a top view in FIG. 6A forming check valve 9. Finally, as
shown in FIGS. 7A and 7B, a second channel layer 42 having a
channel 37 with fluid input 38a and fluid output 38b is aligned
over valve 9 and applied to form the microfluidic device. It is
understood that adhesive layers 25 are applied between substrate.
Representative thicknesses are exaggerated for illustrative
purposes and not for the purpose of depicting actual or relative
layer thicknesses.
[0029] FIGS. 7A-7B and 8A-8B show various embodiments of the
microfluidic devices having multiple channels. A vacuum can be
applied to one or more channels for such devices by pulling fluid
through the microfluidic device. According to the present
invention, the placement of the integral check valve(s) allows the
predictable and desired regulation of fluid flow through the
channels.
[0030] FIG. 9 shows an integrated microfluidic device incorporating
both check valves, 9a and 9b at two different levels of the layered
device having a chamber 54 in layer 55. The substrate 26 on which
the device is fabricated has an electrical coil structure 52
patterned thereon, over which subsequent layers are applied.
Fabrication of the channels and valve structures are carried out as
previously described. After completion of the microfluidic portion
of the device, which includes substrate 26 with patterned
electrical coil structure 52, fluidic channel 20, chamber 54,
valves 9a and 9b, output channel 58, and magnet 56 are applied to
the top of the device and positioned over chamber 54 and coils 52.
Preferably, the magnet may be a molded magnet structure that is
subsequently magnetized in an electric field, or consists of a
permanent magnet that is positioned and preferably held in place by
an adhesive. As will be appreciated by one skilled in the field,
depending upon the polarity applied to the coils 52, a magnetic
field is produced which either attracts or repels the magnet 56,
vertically moving the layers of the device 55, 57, and 59 either
toward or away from the layers 12, 19, and 22, consequently
predictably changing the volume of chamber 54. The volume change
will cause fluid movement through check valves 9a and 9b, resulting
in a pumping action through the microfluidic device. Applying
polarity to the coils in a ramp function or microstep function
versus a large step function will cause the magnet to move more
slowly and consequently cause the chamber to expand or contract
slowly, thus minimizing any damage to cells or other fragile
structures that may be present in the fluid being pumped through
the device.
[0031] Magnet 56 is a micromolded permanent magnet adhered to a
substrate. As will be appreciated by one skilled in the field,
substrate 24 is representative of a variety of substrates that may
comprise movable elements of micromechanical structures. Magnet 56
preferably is a rare earth NdFeB magnet comprising powdered NdFeB
metal suspended in a thermosetting plastic, cured, and magnetized
employing, for example, a magnetic field strength in the order of
about 20 kOe, produced by a suitable electromagnet.
[0032] The fluids presented to the channels and chambers in the
devices of the present invention may comprise an analyte, which is
understood to be a substance or chemical constituent that is
undergoing analysis. Typically, the analyte can be of chemical,
biological or physical nature. Examples of analytes include
molecules, living cells, bacteria, other organisms and fractions of
organisms and tissue, clusters of molecules and atoms,
nanocrystals, etc. In one embodiment, the preferred
diaphragm/magnet assembly is analogous to a heart chamber with the
channels/valves/fluid taking on the role of a circulatory system,
possibly containing cells (e.g. blood). A further embodiment is
contemplated to be useful in modeling a biological system for use
in bio-research, potentially reducing the need for animal
testing.
EXAMPLE
[0033] A flexible structure was made from Kapton.RTM. (polyimide)
as a microfluidic valve component. The Kapton.RTM. structure,
combined with a gold release layer, and an opening to direct fluid
flow, created the reliable integral microfluidic check valve of the
present invention.
[0034] FIG. 3 shows a cross section of a device fabrication where a
Kapton.RTM. layer 22 was laminated onto a Si, glass or plastic
substrate 24. As shown in FIGS. 6A-6B, a patterned gold release
layer 16 was deposited onto the Kapton.RTM. layer surface 22,
followed by the deposition of the layer 12 in which the flap valve
was to be cut. A laser cut "U"shape 14 was made through the flap
layer 12 to the gold release layer 16 forming a flexible structure
with an effective hinge at one end (the base of the "U").
[0035] According to one embodiment, these aforementioned structures
are preferably fabricated out of thermally laminated Kapton.RTM.
structures with laser micro-machining to produce channels and valve
structures, but could be made from any suitable microfluidic system
substrate material as would be understood by one skilled in the
field of microfluidics. For example, if light transmission through
the laminated structure is desired down to 350 nm or below, more
(near UV) transparent films, such as Bayer Apec Polycarbonate,
Solvay Udel, or Radel Polysulfone, or Dyneon THV-220
Fluorothermoplastic can be used in place of the Kapton.RTM. film.
According to one embodiment, each layer is preferably hot press
laminated to the previous laser-machined layer. In this way,
registration of all except the top most layer, is not necessary
during the lamination process. All alignment preferably is done at
the laser operation, such that each laser-machining step is in
registration relative to the previous layers. In this way, the
structure is built up much like an integrated circuit chip rather
than a multi-level circuit board where pre-patterned layers are
pinned together and only laminated as a final step. The top-most
layer, in which a channel has been pre-micro-machined, must be
aligned over the check valve to provide it to a cavity to operate
while also providing a channel for fluid to flow.
[0036] The preferred adhesives used for laminating the multiple
layers used in the microfluidic devices preferably must adhere well
to the underlying substrate on which the fluidic device is
fabricated, and to the layers of material forming the device. They
must be thermally stable during multiple lamination processes. They
must be resistant to the fluids used in the channels during device
operation that might include water of different pH and/or chemical
solvents. Further, the preferred adhesives must be
laser-processable to allow formation of the channels and valves.
Adhesives which can be used for this application preferably include
thermoplastic polymers such as polyimide, polysulfone,
polycarbonate and acrylic materials and blends of such polymers
with cycloaliphatic epoxy with a thermal epoxy curing catalyst
present such that a thermoset layer is formed during lamination.
One preferred adhesive to be used for lamination is a GE developed
material, composed of a siloxane containing polyimide, SPI-135,
available from MicroSi Corp, Phoenix, Ariz., blended with ERL-4221
epoxy, available from Dow Chemical, Midland, Mich. and UV9380C
catalyst, available from General Electric Specialty Materials,
Waterford, N.Y. This adhesive blend has excellent adhesion to
Kapton.RTM., is resistant to attack from water and most solvents,
but releases cleanly from a metal surface, especially a gold
surface.
[0037] The adhesives used in connection with embodiments of the
invention preferably facilitate the use of Kapton.RTM. structures
where selected flaps can move to create micro-fluidic check valves,
when photolithography is used to define small gold areas that act
as release layers.
[0038] The "U"-shaped cuts made in the films of embodiments of the
invention are preferably made with a tripled (355 nm) or quadrupled
(266 nm) YAG laser, or an excimer laser at 308 nm or 248 nm. The
thickness of the layers to be laser-machined may be from about 12
to about 25 .mu.m thick, with the precise thickness dependent upon
the material characteristic, such as, for example, flexibility.
[0039] The layers must have similar properties relative to the
selected adhesive, such as resistance to water and solvents,
thermal stability relative to multiple lamination cycles (to retain
channel integrity), and laser processability. Such preferred
materials include polyimides such as Kapton.RTM., Upilex.RTM. and
Ultem.RTM., high temperature polycarbonates such as Bayer Apec
(especially if clear, transparent and colorless fluidic devices are
desired for possible optical analysis), polysulfone films, PEEK
(polyether ether ketone) and possibly PVDF film made from
Kynar.RTM. plastic, also available from Westlake Plastics.
[0040] While the invention has been described in detail in
connection with only a limited number of embodiments, it should be
readily understood that the invention is not limited to such
disclosed embodiments. Rather the invention can be modified to
incorporate any number of variations, alterations, substitutions or
equivalent arrangements not heretofore described, but which are
commensurate with the spirit and scope of the invention.
Additionally, while various embodiments of the invention have been
described, it is to be understood that aspects of the invention may
include only some of he described embodiments. Accordingly, the
invention is not to be seen as limited by the foregoing
description, but is only limited by the scope of the appended
claims.
* * * * *