U.S. patent application number 14/388323 was filed with the patent office on 2015-02-19 for microfluidic pump.
The applicant listed for this patent is ALERE SAN DIEGO, INC.. Invention is credited to Horst Bossneck, Remus Haupt.
Application Number | 20150050172 14/388323 |
Document ID | / |
Family ID | 49261071 |
Filed Date | 2015-02-19 |
United States Patent
Application |
20150050172 |
Kind Code |
A1 |
Haupt; Remus ; et
al. |
February 19, 2015 |
MICROFLUIDIC PUMP
Abstract
A microfluidic pump is provided for managing fluid flow in
disposable assay devices, which provides constant flows even at
very low flow rates. Devices utilizing the microfluidic pump, as
well as methods for manufacture and performing a microfluidic
process are also provided.
Inventors: |
Haupt; Remus; (Encinitas,
CA) ; Bossneck; Horst; (Jena, DE) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
ALERE SAN DIEGO, INC. |
San Diego |
CA |
US |
|
|
Family ID: |
49261071 |
Appl. No.: |
14/388323 |
Filed: |
March 15, 2013 |
PCT Filed: |
March 15, 2013 |
PCT NO: |
PCT/US13/32020 |
371 Date: |
September 26, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
61615786 |
Mar 26, 2012 |
|
|
|
Current U.S.
Class: |
417/474 |
Current CPC
Class: |
F04B 43/043 20130101;
F04B 43/1246 20130101; F04B 43/12 20130101; F04B 19/006 20130101;
F04B 43/1261 20130101; F04B 43/1292 20130101; F04B 43/14
20130101 |
Class at
Publication: |
417/474 |
International
Class: |
F04B 19/00 20060101
F04B019/00; F04B 43/12 20060101 F04B043/12 |
Claims
1. A pump, comprising: a channel defined by (a) a groove in a first
surface of a first substrate, and (b) a second surface of a second
substrate; and an actuator configured to compress a portion of the
second substrate into the groove of the first substrate without
substantially deforming the groove.
2. The pump of claim 1, wherein the actuator is configured to
translate along an axis of the groove.
3. The pump of claim 1, wherein the groove has a height and the
height is at least about 10 microns, at least about 20 microns, at
least about 30 microns, or at least about 50 microns.
4. The pump of claim 1, wherein the groove has a height and the
height is about 1000 microns or less, about 500 microns or less,
about 250 microns or less, about 125 microns or less, about 100
microns or less, about 75 microns or less.
5. The pump of claim 1, wherein the first and second substrates are
substantially planar.
6. The pump of claim 1, wherein the channel has an inlet and an
outlet and a distance between the inlet and the outlet is at least
about 1 mm, at least about 2.5 mm, at least about 5 mm, at least
about 10 mm, at least about 25 mm.
7. The pump of claim 1, wherein the channel has an inlet and an
outlet and a distance between the inlet and the outlet is about 250
mm or less, 100 mm or less, about 75 mm or less, about 50 mm or
less, about 25 mm or less.
8. The pump of claim 1, wherein the pump is disposed in fluidic
communication with a microfluidic device.
9. The pump of claim 8, wherein the microfluidic device comprises
at least one microchannel configured to receive a liquid sample
suspected of containing at least one target and the microchannel
comprises at least one reagent for use in determining the presence
of the at least one target.
10. The pump of claim 9, wherein the pump is configured to produce
a gas pressure acting upon a distal gas-liquid interface of the
liquid sample when the distal gas-liquid interface of the liquid
sample is disposed within the microchannel of the microfluidic
device.
11. The pump of claim 10, wherein a proximal gas-liquid interface
of the liquid sample is exposed to an ambient atmosphere.
12. The pump of claim 10, wherein the gas pressure acting upon the
distal gas-liquid interface of the liquid sample is less than an
ambient gas pressure.
13. The pump of claim 8, wherein the first and second substrates
are disposed within the microfluidic device.
14. The pump of claim 9, wherein the microchannel of the
microfluidic device comprises the liquid sample disposed
therein.
15. The pump of claim 14, wherein the liquid sample comprises urine
or at least one liquid component of blood.
16. The pump of claim 9, wherein the actuator is configured to
provide a rate of flow of the liquid sample within the microchannel
of the microfluidic device of at least about 1 nl/s, at least about
5 nl/s, at least about 10 nl/s, at least about 25 nl/s, at least
about 50 nl/s, at least about 100 nl/s, at least about 250 nl/s, at
least about 500 nl/s at least about 1000 nl/s.
17. The pump of claim 9, wherein the actuator is configured to
provide a rate of flow of the liquid sample within the microchannel
of the microfluidic device of about 10,000 nl/s or less, about
5,000 nl/s or less, about 2,500 nl/s or less, at least about 1000
nl/s or less.
18. The pump of claim 9, wherein a total volume of liquid sample
within the microchannel is about 100 microliters or less, about 50
microliters or less, about 25 microliters or less, about 20
microliters or less.
19. The pump of claim 1, wherein the channel has an uncompressed
area and, when compressed by the actuator, the compressed portion
of the second substrate occludes at least about 50%, at least about
75%, at least about 90%, at least about 95%, at least about 97.5%,
at least about 99%, or essentially all of the uncompressed area of
the channel.
20. The pump of claim 1, wherein in the uncompressed state, the
groove has a width and the width is at least about 50 microns, at
least about 100 microns, at least about 200 microns, at least about
500 microns.
21. The pump of claim 20, wherein, in the compressed state, the
width of the groove is at least about 75%, at least about 90%, at
least about 95%, at least about 97.5%, at least about 99%, or
essentially the same as in the uncompressed state.
22. The pump of claim 1, wherein, in the compressed state, the
groove has a width and the width is about 2000 microns or less,
about 1500 microns or less, about 1000 microns or less, about 750
microns or less about 600 microns or less.
23. The pump of claim 22, wherein, in the compressed state, the
height of the groove is at least about 75%, at least about 90%, at
least about 95%, at least about 97.5%, at least about 99%, or
essentially the same as in the uncompressed state.
24. The pump of claim 1, wherein, in the uncompressed state, the
second substrate has a first thickness overlying the groove and a
second thickness spaced apart laterally a first distance from the
groove and wherein the second thickness is at least about 110%, at
least about 125%, at least about 150%, at least about 175%, or at
least about 200% greater than the first thickness.
25. The pump of claim 24, wherein the first distance is at about
50% greater than a width of the groove, about 75% greater than a
width of the groove, about 100% greater than a width of the groove,
about 200% greater than a width of the groove.
26-167. (canceled)
Description
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The invention relates to microfluidics technology, and more
particularly to a microfluidic pump for control of fluid flow
through microchannels.
[0003] 2. Background Information
[0004] Microfluidics systems are of significant value for acquiring
and analyzing chemical and biological information using very small
volumes of liquid. Use of microfluidic systems can increase the
response time of reactions, minimize sample volume, and lower
reagent and consumables consumption. When volatile or hazardous
materials are used or generated, performing reactions in
microfluidic volumes also enhances safety and reduces disposal
quantities.
[0005] Microfluidic devices have becoming increasingly important in
a wide variety of fields from medical diagnostics and analytical
chemistry to genomic and proteomic analysis. They may also be
useful in therapeutic contexts, such as low flow rate drug
delivery.
[0006] The microcomponents required for these ends are often
complex and costly to produce. For example, a micropump may be used
to mix reagents and transport fluids between a disposable analysis
platform component of the system and an analysis instrument (e.g.,
an analyte reader with display functions). Yet controlling the
direction and rate of fluid flow within the confines of a
microfluidic device, or achieving complex fluid flow patterns
inside microfluidic channels is difficult.
SUMMARY OF THE INVENTION
[0007] A microfluidic pump has been developed in order to provide
low cost, high accuracy means for onboard sample handling in
disposable assay devices. Devices utilizing the microfluidic pump,
as well as methods for manufacture and performing a microfluidic
process are also provided.
[0008] Accordingly, in one aspect, the present invention provides a
microfluidic pump module. In one embodiment, the microfluidic pump
module includes a first plate element and a second plate element,
the first plate element being elastomeric and the second plate
element being non-elastomeric. The second plate element includes a
microchannel formed on a surface of the second plate element, and
the first and second plate elements are coupled to form a fluid
tight seal along the boundary of the microchannel defining a fluid
flow path.
[0009] In another aspect, the invention provides a microfluidic
device utilizing the microfluidic pump module described herein. The
microfluidic device includes (a) a rigid substrate having a
microchannel formed on a surface thereof; and (b) a flexible layer
coupled to and overlying the rigid substrate thereby enclosing the
microchannel, wherein the flexible layer comprises a raised element
disposed over a portion or all of the microchannel. The device
further includes a fluid tight seal formed between the rigid
substrate and the flexible layers along a periphery of the
microchannel forming an enclosed capillary.
[0010] In another aspect, the invention provides a microfluidic
device utilizing the microfluidic pump module described herein. The
microfluidic device includes (a) a rigid substrate having a
microchannel formed on a surface thereof; and (b) a flexible layer
coupled to and overlying the rigid substrate thereby enclosing the
microchannel, wherein the flexible layer has a flat surface
disposed over a portion or all of the microchannel. The device
further includes a fluid tight seal formed between the rigid
substrate and the flexible layers along a periphery of the
microchannel forming an enclosed capillary.
[0011] In a further aspect, the invention provides a microfluidic
device utilizing the microfluidic pump module described herein,
wherein the pump module comprises at least two independent
microchannels arranged in a substantially parallel manner. One or
more actuators are provided which act upon the two or more
microchannels simultaneously, thereby providing means to pump two
fluids separate from one another. In some embodiments the
microchannels have identical cross sectional areas, such that the
volume of fluid transported per unit distance of the microchannel
is substantially the same. In other embodiments the at least two
microchannels have different cross sectional areas, in which
instance the volume of fluid transported per unit distance of the
microchannel is different.
[0012] In still a further aspect, the invention provides a
microfluidic device utilizing the microfluidic pump module
described herein, wherein the pump module comprises at least two
independent microchannels arranged concentrically about a point
upon which at least one actuator rotates. In such embodiment where
the at least two microchannels have identical cross sectional area,
per revolution of the at least one actuator, a greater volume of
fluid will be transported in the outermost channel according to the
equation Q=r.omega.A, where Q is the volume flow rate, r is the
radius of the microchannel, w is the angular velocity and A is the
cross sectional area of the microchannel. Thus if the outermost
channel has a radius r2, which is three times the radius of the
inner most channel r1, then three times the volume of fluid will be
transported in the outermost channel compared with the innermost
channel per revolution of the actuator. The skilled person will
thus readily recognize that by altering the relative ratio of cross
sectional area of the respective concentric microchannels,
different volumes of fluid may be transported per revolution in
each respective channel
[0013] In another aspect, the invention provides a method for
performing a microfluidic process. The method includes (a) applying
a voltage to a microfluidic pump module as described herein. The
applied voltage activates a motor which advances an actuator
element, such as one or more rollers, which is rotatably engaged
with the second substrate, causing deformation of the second
substrate into the microchannel formed on the surface of the first
substrate. Deformation of the elastomeric second substrate into the
microchannel forces fluid within the microchannel along the
microchannel resulting in a fluid flow. The first substrate is
formed from a material having a Shore D hardness of between about
75 and about 90. Such materials include, but are not limited to,
polystyrene, polypropylene, polymethylmethacrylate, polycarbonate
and the like. The microchannel or groove formed in the surface of
the first substrate is dimensionally stable, by which is meant that
when the second substrate is deformed into the groove in the first
substrate, the width of the groove is at least about 75%, at least
about 90%, at least about 95%, at least about 97.5%, at least about
99%, or essentially the same as in the uncompressed state and
height the groove is at least about 75%, at least about 90%, at
least about 95%, at least about 97.5%, at least about 99%, or
essentially the same as in the uncompressed state. The dimensions
of the groove are thus considered to be essentially unchanged as a
consequence of the deformation of the second substrate into the
first substrate, The second substrate is formed from a material
having a Shore A hardness of between about 15 and 90. Such
materials include, but are not thermoplastic elastomer (TPE),
polydimethylsiloxane (PDMS), silicone rubber, fluoroelastomer and
the like. Such materials are considered to be dimensionally
unstable, by which is meant that when a compressive force or a
stretching force is applied to such polymeric materials the
material deforms, either through elongation in one or more
directions, or the material compresses in one or more
dimensions.
[0014] In another aspect, the invention provides a method of
manufacturing a microfluidic device. The method includes coupling a
rigid substrate having a microchannel formed on a surface thereof,
to a flexible layer overlying the rigid substrate and enclosing the
microchannel. A fluid tight seal is formed between the rigid
substrate and the flexible layers along a periphery of the
microchannel forming an enclosed capillary. The rigid substrate and
the flexible layer are coupled via a laser welding process. The
process includes:
[0015] (a) exposing one of the rigid substrate or the flexible
layer to ultra violet laser energy around the periphery of the
microchannel so as to carbonize the surface of the rigid substrate
or the flexible layer;
[0016] (b) applying a compressive force between the rigid substrate
and the flexible layer; and
[0017] (c) exposing the compressed rigid substrate and the flexible
layer to infra red laser energy to cause localized heating and
melting in the proximity of the carbonized surface of (a) so as to
seal the rigid substrate and the flexible layer, thereby forming a
fluid tight seal along the boundary of the microchannel.
[0018] In another aspect the invention provides a method of
manufacturing a microfluidic device. The method includes coupling a
rigid substrate having a microchannel formed on a surface thereof,
to a flexible layer overlying the rigid substrate and enclosing the
microchannel. A fluid tight seal is formed between the rigid
substrate and the flexible layers along a periphery of the
microchannel forming an enclosed capillary. The rigid substrate and
the flexible layer are coupled via a process of over-molding. The
process includes:
[0019] (a) injecting a first polymer composition into an injection
mold cavity to form the rigid substrate;
[0020] (b) injecting a second polymer composition into an injection
mold cavity to form the flexible layer; and
[0021] (c) causing the molten second polymeric material to fuse
with the first polymeric material introduced in (a) so as to seal
the rigid substrate and the flexible layer, thereby forming a fluid
tight seal along the boundary of the microchannel.
BRIEF DESCRIPTION OF THE DRAWINGS
[0022] FIG. 1 is a series of schematics illustrating movement of
various components during operation of a microfluidic device in
embodiments of the invention.
[0023] FIG. 1A is a cross-sectional view of a portion of a
microfluidic device in embodiments of the invention.
[0024] FIG. 1B is a cross-sectional view of a portion of a
microfluidic device in embodiments of the invention.
[0025] FIG. 2 is a cross-sectional view of a portion of a
microfluidic device in embodiments of the invention.
[0026] FIG. 3 is a perspective view of a portion of a microfluidic
device in an embodiment of the invention.
[0027] FIG. 4 is a top view of a portion of a microfluidic device
in an embodiment of the invention.
[0028] FIG. 5 is a perspective view of a microfluidic device in an
embodiment of the invention.
[0029] FIG. 6 is a series of schematics illustrating a microfluidic
device in embodiments of the invention.
[0030] FIG. 6A is a top view of a microfluidic device in an
embodiment of the invention.
[0031] FIG. 6B is a top view of a microfluidic device in an
embodiment of the invention.
[0032] FIG. 6C is a top view of a microfluidic device in an
embodiment of the invention.
[0033] FIG. 7 is a graphical representation depicting data
generated with a microfluidic device in an embodiment of the
invention.
[0034] FIG. 8 is a graphical representation depicting data
generated with a microfluidic device in an embodiment of the
invention.
[0035] FIG. 9 is a graphical representation depicting data
generated with a microfluidic device in an embodiment of the
invention.
[0036] FIG. 10 is a top view of a portion of a microfluidic device
in an embodiment of the invention.
[0037] FIG. 11 is a cross-sectional schematic of a drive for use in
one embodiment of the invention.
[0038] FIG. 12 is a cross-sectional schematic of a drive for use in
one embodiment of the invention.
[0039] FIG. 13 is a top view schematic of a microfluidic device in
an embodiment of the invention.
DETAILED DESCRIPTION OF THE INVENTION
[0040] A microfluidic pump and device containing the pump have been
developed in order to provide, in embodiments, low cost, high
accuracy and low flow rate means for onboard sample handling for
disposable assay devices. Advantageously, the rate of fluid flow
within the pump is essentially constant even at very low flow
rates.
[0041] The pump comprises a first substrate and a second substrate
secured with respect to one another to provide a structure having
one or more microchannels which are sealed along the boundaries of
the microchannels thereby defining fluid flow paths.
[0042] With reference to FIGS. 1A and 1B, one or more microchannel
structures (40), e.g., grooves, are formed in a major surface of a
first substrate (20) formed, e.g., of a non-elastomeric or rigid
material. A deformable second substrate (10) formed, e.g., of an
elastomer, is secured with respect to first substrate 20 to create
enclosed microchannels (40) having a fluid tight seal along their
boundaries. When a force, for example via a deformation element
such as roller (50), is applied to the elastomer material (10), at
least of portion of the second substrate is compressed into the
microchannel (40) of the non-elastomeric (20) component thereby
occluding at least a portion of the microchannel (40) at the site
of compression.
[0043] In the compressed state, the second substrate typically
occludes a sufficient portion of the microchannel (40) to displace
a substantial portion of fluid from microchannel (40) at the site
of compression. For example, the second substrate may occlude a
sufficient portion of the microchannel (40) to separate fluid
disposed within microchannel (40) on one side of the site of
compression from fluid disposed within microchannel (40) on the
other side of the site of compression. In embodiments, the second
substrate occludes, in the compressed state, at least about 50%, at
least about 75%, at least about 90%, at least about 95%, at least
about 97.5%, at least about 99%, or essentially all of the
uncompressed cross-sectional area of the groove at the site of
compression.
[0044] The compression may create a fluid-tight seal between the
first and second substrates within the groove at the site of
compression. When a fluid-tight seal is formed, fluid, e.g., a
liquid, is prevented from passing along the groove from one side of
the site of compression to the other side of the site of
compression.
[0045] The fluid-tight seal may be transient, e.g., the second
substrate may fully or partially relax upon removal of the
compression thereby fully or partially reopening the groove.
[0046] The groove has a first cross-sectional area in an
uncompressed state and a second cross-sectional area in the
compressed state. In embodiments, the portion of the elastomer is
compressed into the groove without substantially deforming the
groove. For example, a ratio of the cross-sectional area at the
site of compression in the compressed state to the cross-sectional
area at the same site in the uncompressed state may be at least
about 0.75, at least about 0.85, at least about 0.925, at least
about 0.975, or about 1. In embodiments, the height of the groove,
e.g., the maximum height of the groove at the site of compression,
in the compressed state may be at least about 75%, at least about
85%, at least about 90%, at least about 95%, or about 100% of the
height of the groove at the same site in the uncompressed state. In
embodiments, the width of the groove, e.g., the maximum width of
the groove at the site of compression, in the compressed state may
be at least about 75%, at least about 85%, at least about 90%, at
least about 95%, or about 100% of the width of the groove at the
same site in the uncompressed state.
[0047] Translation of the site of compression along the length of
the microchannel (40) creates an effective pumping action resulting
in flow of fluid within the microchannel (40) in the direction of
the advancing deformation element (50). In some embodiments a
raised element (30), such as a bump, is present on the elastomer
(10), which may be placed over the microchannel region (40),
thereby increasing the thickness of elastomeric material which may
aid sealing of the elastomer into the channel when compressed
against the non-elastic component (20). For example, in the
uncompressed state, the elastomer may have a first thickness
overlying the groove and a second thickness spaced apart laterally
a first distance from the center of the groove. In embodiments, the
second thickness is at least about 110%, at least about 125%, at
least about 150%, at least about 175%, or at least about 200%
greater than the first thickness. The second thickness may be at
least about 500% or less, about 400% or less, about 300% or less,
or at about 250% or less greater than the first thickness.
[0048] The first distance may be at least about 1 mm, at least
about 2.5 mm, at least about 5 mm, or at least about 1 cm. The
first distance may be about 2.5 cm or less, about 2 cm or less,
about 1.5 cm or less, or about 1.25 cm or less. In embodiments, the
first distance is at about 1.5 times greater, about 1.75 times
greater, about 2 times greater, or about 4 times greater than a
width, e.g., a maximum width, of the groove. The first distance may
be about 25 times greater or less, about 20 times greater or less,
about 15 times greater or less, or about 10 times greater or less
than a width, e.g., a maximum width, of the groove.
[0049] In one aspect, a microfluidic pump module (100) is provided
utilizing the microfluidic structure described herein. Again with
reference to FIGS. 1A and 1B, the microfluidic pump module (100)
includes a first elastomeric plate element (10) and a second rigid
plate element (20). The second plate element (20) includes a
microchannel (40) formed on a surface of the second plate element
(20), and the first and second plate elements are coupled to form a
fluid tight seal along the boundary of the microchannel (40)
defining a fluid flow path.
[0050] In another aspect, the invention provides a microfluidic
device (100) utilizing the microfluidic pump module described
herein. Again with reference to FIGS. 1A and 1B, the microfluidic
device (100) includes a rigid substrate (20) having a microchannel
(40) formed on a surface thereof and a flexible layer (10) coupled
to and overlying the rigid substrate (20) thereby enclosing the
microchannel (40).
[0051] In yet a further aspect, the invention provides a
microfluidic device (100), which again with reference to FIGS. 1A
and 1B, the reverse orientation is provided. In this instance
microchannel (40) is formed in flexible layer (10); and rigid
substrate (20) is provided with a flat surface profile, such that
when flexible layer (10) is coupled to and overlying rigid
substrate (20) a microchannel (40) is formed therebetween.
[0052] In various embodiments, the flexible layer (10) comprises a
raised element (30) disposed over a portion or all of the
microchannel (40). The raised element (30) provides an increased
cross-section thickness in the area which coincides with the
microchannel (40). This assists in creating a water tight seal
between the deformed elastomeric material (60) advanced into the
microchannel (40) with the surface of the microchannel. One skilled
in the art would understand that the raised element (30) may be one
of a number of suitable shapes such as a bump. In other
embodiments, flexible layer (10) has no raised element (30), in
which case microchannel (40) is covered entirely by flexible layer
(10) which has a flat upper surface profile, which surface is not
in contact with rigid substrate (20).
[0053] One or more microchannels (40) may be formed on a surface of
the rigid substrate (20) by any number of suitable techniques known
in the art. For example, microchannels may be formed by deposition
of materials through a mask, chemical etching, laser etching,
molding of a plastic substrate, and the like. A fluid tight seal is
also formed between the rigid substrate (20) and the flexible layer
(10) along a periphery of the microchannel (40) forming an enclosed
capillary having a defined fluid flow path.
[0054] Microchannels may be dimensioned to define the volume within
the microchannel and resultant flow rate for a given rate at which
the elastomer is progressively deformed into the microchannel. The
high quality and precision of the so formed microchannel results in
a microfluidic pump element that can achieve very slow and
consistent flow rates, which may not otherwise be achieved if
alternate processes of manufacture were employed. A microchannel
may be dimensioned such that it has a constant width dimension and
a constant depth dimension along all or a portion of its length. In
one embodiment, a microchannel will have a constant width dimension
and a constant depth dimension along a length of the microchannel
which engages a deformation element. In general, a microchannel has
a width dimension of between 500 to 900 microns and a depth
dimension of between 40 to 100 microns. As such, the device may be
adapted for a flow rate within the microchannel of between 0.001
.mu.l/s to 5.0 .mu.l/s.
[0055] Microchannels having a variety of cross-sectional geometries
may be utilized. FIGS. 1A and 1B depict a microchannel (40) in
which the bottom surface of the microchannel is arced and defines a
concave circular geometry. However, it will be understood that the
microchannel (40) may have a rounded, elliptical or generally U
shaped bottom. In one embodiment, the microchannel has an arced
shaped bottom having a radius of curvature of between 0.7 and 0.9
mm. FIG. 2 is a cross-sectional view of a portion of a microfluidic
device in one embodiment of the invention in which specific
dimensions (shown in mm) are described for various features.
[0056] One skilled in the art would appreciate that the surfaces of
microchannels (40) may be modified, for example by varying
hydrophobicity. For instance, hydrophobicity may be modified by
application of hydrophilic materials such as surface active agents,
application of hydrophobic materials, construction from materials
having the desired hydrophobicity, ionizing surfaces with energetic
beams, and/or the like.
[0057] As discussed herein, a device of the present invention may
include a plurality of microchannels (40), each having various
geometries and disposed on the rigid substrate (20) (or in the
alternate on the flexible layer (10)) in a variety of patterns. For
example, microchannels (40) may be linear or extend arcuately along
the surface of the rigid substrate (20). FIGS. 3 and 4 illustrate
microchannels (40) being disposed as generally circular or spiral
geometries. FIG. 3 is a perspective view of a device in which
microchannels (40) are disposed as spirals, a smaller volume
microchannel disposed within a microchannel having a larger volume.
FIG. 4 is a top view of a device in which the microchannel (40) is
disposed in a spiral manner having ports (100) and (110) which may
be in fluid communication with one or more additional microchannels
or structures. In one embodiment, the circular or spiral portion of
the microchannel has a length of between 20 to 100 mm.
[0058] A spiral or generally circular shaped microchannel allows
for fluid to be advanced through the microchannel of the pump
module or device by a deformation element (50) that is radially
coupled to the device. FIG. 5 is an illustration depicting a pump
module and device of the present invention in which multiple
deformation elements (50) are radially coupled and configured to
engage a microchannel having a circular or spiral geometry. The
deformation elements (50) are provided in a housing (80) configured
to radially traverse one or more microchannels provided on the
microfluidic laminate structure (110) when the structure is placed
in contact with the deformation elements (50) (spiral microchannel
is disposed on the opposite side of laminate structure (110)
shown). As will be appreciated by those of skill in the art, the
rotational direction of the deformation elements (50) with relation
to the microfluidic laminate structure (110) dictates the direction
of flow within the microchannel. As such, one skilled in the art
would appreciate that, advantageously, fluid flow through the pump
may be bidirectional.
[0059] Housing (80) may be rotated by applying a voltage to a motor
controlling movement thereof. As such, the invention further
provides a method for performing a microfluidic process which
includes applying a voltage to a device as described herein. The
applied voltage activates a motor which advances at least one
deformation element (50), such as one or more rollers, which are
rotatably engaged with the elastomeric first plate element (10),
causing deformation of a raised element (30) on the flexible layer
(10) into the microchannel (40) formed on the surface of the rigid
substrate (20).
[0060] A wide range of pulses per second may be applied to the
electrical motor thereby effectuating a wide range of flow rates
within microchannels The fluid flow is essentially constant, with
little or no shear force being imposed on the fluid, even at very
low flow rates. These characteristics of the pump enhance the
accuracy of analyses performed with it (e.g., analyte integrity is
preserved by minimizing exposure of sample components to shear and
degradation), while low flow rates provide sufficient time for
chemical reactions to occur. A low, constant pumped flow rate can
also be very useful in drug delivery, to ensure dosing
accuracy.
[0061] In one embodiment, between 100 and 10,000 pulses per second
may be applied resulting in a flow rate of between 0.001 .mu.l/s to
5.0 .mu.l/s through microchannels. The design of the present
invention allows forces within microchannels of the present
invention to remain fairly constant over a wide range of applied
pulses.
[0062] For example, FIGS. 7-9 are graphs plotting forces generated
within microchannels as a function of the number of pulses per
second. As depicted in the graphs of FIGS. 7-9, forces generated
within the microchannels are relatively constant over a wide range
of pulses per second indicating substantially constant flow with
minimal shear.
[0063] FIGS. 6A-6C illustrate various configurations in different
embodiments of the invention in which at least one spiral or
circular microchannel is provided. Circular or spiral microchannels
(40) may be disposed such that they are in fluid communication with
one or more additional microchannels (140) through ports (100) and
(110). Additional microchannels (140) may be provided with various
reagents, immobilized therein or otherwise provided such that a
biological assay may be performed on a fluid sample.
[0064] With reference to FIG. 1, as discussed herein, a fluid tight
seal is formed between the rigid substrate (20) and the flexible
layer (10) along a periphery of the microchannel (40) forming an
enclosed capillary having a defined fluid flow path. FIG. 10,
illustrates a portion of a device having a generally spiral
microchannel in which a fluid tight seal (140) is shown along the
periphery of the microchannel (40).
[0065] A variety of methods may be utilized to couple rigid
substrate (20) to the elastomer that forms flexible layer (10). The
parts may be joined together using UV curable adhesive or other
adhesive that permits for movement of the two parts relative one
another prior to curing of the adhesive/creation of bond. Suitable
adhesives include a UV curable adhesive, a heat cured adhesive, a
pressure sensitive adhesive, an oxygen sensitive adhesive, and a
double-sided tape adhesive.
[0066] Alternatively, the parts may be coupled utilizing a welding
process. Such processes including an ultrasonic welding process, a
thermal welding process, and a torsional welding process.
[0067] In a further alternative, the parts may be joined using a
process of two-shot molding or overmolding, in which case first one
polymer and then the other is injected into a mold tool. One of
skill in the art will readily appreciate that elastomeric and
non-elastomeric polymers can be joined in this way to achieve fluid
tight seals between the parts.
[0068] In one embodiment a process of laser welding is utilized.
The process includes:
[0069] (a) exposing one of the first or second plate elements to
ultra violet laser energy around the periphery of the microchannel
so as to carbonize the surface of the first or second plate
element;
[0070] (b) applying a compressive force between the first and
second plate elements; and
[0071] (c) exposing the compressed first and second plate elements
to infra red laser energy to cause localized heating and melting in
the proximity of the carbonized surface of (a) so as to seal the
first and second plate elements, thereby forming a fluid tight seal
along the boundary of the microchannel.
[0072] The benefits of such approaches mean that (i) the parts may
be manipulated (slid against one another) during manufacture to
achieve desired alignments, (ii) intricate forms can be achieved in
the non-elastomer--linear or arcuate channels (or combinations
thereof) with a plurality of channel geometries, (iii) connections
with the device may be made via the non-elastomeric material, which
is dimensionally stable.
[0073] In various embodiments, additional microchannels and
structures may be provided to allow the device to perform a number
of different types of biological assays or reactions. For example,
additional fluid or reagent reservoirs may be provided, one or more
of which act as a reaction chamber for example. Additional
structure and depicted in the following example which is intended
to illustrate but not limit the invention.
[0074] The following embodiment describes the use of a planar
circular or spiral peristaltic pump of the present invention for
use in low cost diagnostic products consisting of an instrument and
consumable, where the consumable requires sealing due to a
potential high risk of contamination.
[0075] Two aspects are described. First, a very low cost method to
perform pumping a liquid sample to stored dry chemicals which are
deposited at a location internal to the consumable, followed by
mixing of the liquid sample with the stored chemicals. Second,
dilution of chemicals using the same active pumping system where
the dilution step occurs part way through the diagnostic
process.
[0076] The two aspects may be used together or individually. They
shall now be described separately with reference to FIGS. 11-13.
Reference numerals for features of FIGS. 11-13 as used in this
Example are specific for each Figure and may be represented by
another numeral in FIGS. 1-10 of this application.
[0077] With reference to FIG. 11, the method to perform pumping
sample fluids to deposited chemicals followed by mixing of sample
fluid with deposited chemicals in a low cost manner involves using
only one actuator, for example a DC or stepper motor (1)
incorporated into the instrument. The peristaltic pump consists of
a planar circular or spiral annular microchannel (2) as a feature
of a substrate (3) of the consumable (4) and the deforming membrane
of the pump is provided by an elastomeric layer (5) which is
deformed by the pump rollers (6). Concentric to the annular pump
channels is the mixing chamber (7) which contains a magnetic or
magnetized puck (8). Concentric to the pump rollers of the
instrument is a structure comprising a mixing head (9) which is
magnetic or magnetized and is magnetically coupled to the puck.
[0078] By providing inlet and outlet ports to the mixing chamber
from the pump microchannels, the pump and mixing chamber are
fluidically connected, thus fluid can be pumped from the pump
microchannels into the mixing chamber as the motor rotates in a
predetermined direction. The instrument component of the pump
comprises a suitable mechanism to provide pumping and mixing
functionality when the motor is rotated in a certain direction, but
only mixing functionality when the motor is rotated in the opposite
direction, for example a ratchet system implemented by a pawl (10)
and a compression spring (11) whereby the mixing head rotates with
the pump rollers in one rotational direction of the motor and
whereby the pump rollers disengage from the motor when the motor
rotates in the other direction, thus providing rotation of the
mixing head only. The compression spring may also provide the
necessary contact force on the pump channels to facilitate
effective pumping. A sequence of events is provided in Table 1
below.
TABLE-US-00001 TABLE 1 Motor Operation Effect on fluid Motor Pump
rotor is engaged and sample fluid is transported from rotates one
location on the consumable into the mixing chamber. clockwise
Magnetic force to the puck is also provided. Motor Transportation
of sample fluid is stopped. stops Motor Pump rotor is disengaged
and sample fluid remains in mixing rotates chamber. Only the puck
moves due to magnetic force and counter sample is mixed with
deposited chemicals. clockwise Motor Pump rotor is engaged and
chemicals mixed with sample rotates fluid are transported from the
mixing chamber to another clockwise location on the consumable.
[0079] Another embodiment provides an annular mixing chamber
internal or external to the pump channels. This embodiment could
feasibly be produced at a lower cost than the first embodiment and
is described with reference to FIG. 12. The spiral or circular pump
channel (1) as a feature in a substrate (2) is overlaid with an
elastomeric membrane (3) and deformed by pump rollers (4) in a
similar manner to that described in FIG. 11. However, in this
particular embodiment the mixing chamber is an annular channel (4)
as a concentric feature to the pump channel but located on the
reverse face of the pump channel substrate.
[0080] Located within this annular channel is one or many bearing
balls (5) which are magnetically coupled to a magnetic or
magnetized element on the rotor (6) such that as the rotor rotates
the bearing balls also rotate in the annular channel, thus
providing mixing of chemicals initially deposited inside the
annular channel. The drive mechanism to achieve mixing and pumping
in one rotational direction of the motor and just mixing in the
other rotational direction of the motor is envisaged to be similar
to that described with reference to FIG. 11.
[0081] With reference to FIG. 13 and including features of the
motor drive system described in the sections above, the method to
perform a dilution step during the diagnostic test using the
circular or spiral peristaltic pump is described: Two concentric
circular or spiral pump channels, are included in the consumable
each having their own fluid path, for example, the inner
microchannel (1) provides fluidic pumping of the sample fluid (2)
and the outer microchannel (3) provides fluidic pumping for a
dilution fluid (4). Each microchannel shares the same pump rollers
(5), such that rotation of the drive shaft by the low cost motor
causes both sample fluid and buffer fluid to be pumped.
[0082] Should more fluids be required to be pumped in separate
channels, this peristaltic pump can be designed to accommodate
multiple fluidic channels on different radii if desired. In this
embodiment the sample that is transported is first required to be
mixed with stored deposited chemicals (6) located within the mixing
chamber (7), followed by a dilution step using a dilution
fluid.
[0083] It is preferable to store the dilution fluid away from the
stored chemicals so the stored chemicals do not become affected by
the dilution fluid. When the motor rotates in a certain direction
the pump rollers engage with the pumping membrane to transport both
sample fluid and dilution fluid into the consumable, as the mixing
chamber fills with sample fluid, the dilution fluid fills a
secondary chamber (8) which is sized according to the amount of
dilution fluid required and the geometry of the dilution fluid
pumping channels and the mixing chamber volume. When the motor
stops both dilution fluid and sample fluid remain in their
respective chambers.
[0084] If mixing is required, an equivalent mechanism as described
above could be implemented which rotates the motor in the opposite
direction to only provide mixing. When the sample fluid and
dilution fluid are required to be combined, the motor rotates to
engage the pump rollers which transport the sample and dilution
fluid to a location inside the consumable which combines the two
fluids (9). To assist combining the two fluids, passive mixing
features (10) may be included at the fluid combining region. As the
motor continues to rotate to pump the two fluids, the diluted
sample can be transported to another location on the consumable,
for example a location to carry out detection of an analyte
(11).
[0085] Several advantages are provided by the invention. First,
manufacturing costs are lowered due to the function and form of the
circular or spiral peristaltic pump design. Aspects of the pump
design which make this possible are circular or spiral geometry
allows for the use of only one actuator; in this embodiment it is
an electric motor, such that rotating the motor in one direction
performs a different function to rotating the motor in the opposite
direction. An additional feature of the pump design is the ability
for the consumable part of the pump to include multiple pump
channels such that multiple fluids may be transported using the
same motor drive mechanism.
[0086] If a chemical reaction, such as an amplification reaction,
is performed which could result in contamination, or if the
potential for contamination is to be removed for other reasons,
then the pump design allows the pump to be sealed to the
environment.
[0087] A wide range of pulses per second may be applied to the
electrical motor thereby effectuating a wide range of flow rates
within microchannels, including very low flow rates. The fluid flow
is essentially constant, with little or no shear force being
imposed on the fluid, even at very low flow rates. These
characteristics of the pump enhance the accuracy of analyses
performed with it (e.g., analyte integrity is preserved by
minimizing exposure of sample components to shear and degradation),
while low flow rates provide sufficient time for chemical reactions
to occur. A low, constant pumped flow rate can also be very useful
in drug delivery, to ensure dosing accuracy.
[0088] Although the invention has been described it will be
understood that modifications and variations are encompassed within
the spirit and scope of the invention. Accordingly, the invention
is limited only by the following claims.
* * * * *