U.S. patent application number 11/053819 was filed with the patent office on 2005-07-07 for implementation of microfluidic components in a microfluidic system.
This patent application is currently assigned to Cytonome, Inc.. Invention is credited to Deshpande, Manish, Gilbert, Johh Richard.
Application Number | 20050145497 11/053819 |
Document ID | / |
Family ID | 31982303 |
Filed Date | 2005-07-07 |
United States Patent
Application |
20050145497 |
Kind Code |
A1 |
Gilbert, Johh Richard ; et
al. |
July 7, 2005 |
Implementation of microfluidic components in a microfluidic
system
Abstract
A system and method for integrating microfluidic components in a
microfluidic system enables the microfluidic system to perform a
selected microfluidic function. A capping module includes a
microfluidic element for performing a microfluidic function. The
capping module is stacked on a microfluidic substrate having
microfluidic plumbing to incorporate the microfluidic function into
the system.
Inventors: |
Gilbert, Johh Richard;
(Brookline, MA) ; Deshpande, Manish; (Canton,
MA) |
Correspondence
Address: |
LAHIVE & COCKFIELD, LLP.
28 STATE STREET
BOSTON
MA
02109
US
|
Assignee: |
Cytonome, Inc.
Watertown
MA
|
Family ID: |
31982303 |
Appl. No.: |
11/053819 |
Filed: |
February 8, 2005 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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11053819 |
Feb 8, 2005 |
|
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10329018 |
Dec 23, 2002 |
|
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6878271 |
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60409489 |
Sep 9, 2002 |
|
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60410685 |
Sep 13, 2002 |
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Current U.S.
Class: |
204/600 |
Current CPC
Class: |
B01L 2300/047 20130101;
B01L 2300/041 20130101; B01L 3/50273 20130101; B01L 3/502738
20130101; B01L 2200/146 20130101; B01L 2400/0666 20130101; B01L
3/06 20130101; B01L 3/502707 20130101; B01L 2400/0481 20130101;
B01L 2200/027 20130101; B01L 3/502715 20130101; C30B 29/58
20130101; B01L 2200/028 20130101; B01L 2400/0655 20130101; C30B
7/00 20130101; B01L 2300/0681 20130101 |
Class at
Publication: |
204/600 |
International
Class: |
G01N 027/453 |
Claims
1. A microfluidic system, comprising: a first microchannel formed
in a substrate; a first communication port coupling the first
microchannel to a surface of the substrate; and a capping module
having a microfluidic element for performing a microfluidic
function, wherein the capping module is adapted to be stacked on
the substrate and placed in communication with the microchannel to
introduce the microfluidic function into the microfluidic
system.
2. The system of claim 1, further comprising a second communication
port connecting a second microchannel to a surface of the
substrate.
3. The system of claim 2, wherein the capping module includes a
chamber for coupling the first microchannel to the second
microchannel.
4. The system of claim 1, wherein the microfluidic element
comprises a membrane.
5. The system of claim 1, wherein the microfluidic element
comprises one of a valve for regulating fluid flow through the
microchannel, a pressure sensor and a microfluidic pump.
6. The system of claim 1, wherein the capping module is bonded to
the substrate to integrate the microfluidic function into the
microfluidic system.
7. The system of claim 1, wherein the capping module has a
cross-sectional dimension of between about 1 millimeter and about 5
centimeters.
8. The system of claim 2, wherein the capping module further
includes a membrane for selectively blocking said communication
port, and an actuator assembly for controlling a position of the
membrane.
9. The system of claim 1, wherein the capping module has a recess
and a membrane covering the recess to form a chamber, wherein the
cap is adapted to be assembled on the substrate such that the
membrane covers the first communication port.
10. The system of claim 1, wherein the capping module includes: a
membrane for separating a substance into a first and second
component; a first flow path for transmitting a substance; a first
reservoir disposed above the membrane and in communication with the
first flow path for receiving the substance.
11. The system of claim 10, wherein the substrate forms a second
flow path for receiving the second component of the substance and
the substrate forms a second reservoir below the membrane for
receiving the first component of the substance when the capping
module is stacked thereon.
12. The system of claim 11, further comprising a first flow source
in communication with the first fluid path for inducing a flow in
the substance.
13. The system of claim 1, wherein the substrate has a plurality of
microchannels formed therein, wherein each microchannel includes
one or more communication ports for connecting the microchannel to
a surface of the substrate.
14. The system of claim 13, further comprising a plurality of
microfluidic capping modules, each having associated therewith a
microfluidic element for performing a microfluidic function, one or
more of said microfluidic capping modules for placement on the
substrate in fluid communication with one or more of the
microchannels to incorporate the associated microfluidic function
into the system.
15. A capping module for a microfluidic system, comprising: a
substrate; and a microfluidic element disposed on the substrate for
performing a microfluidic function, wherein the capping module is
adapted to be stacked on a microfluidic system having a
microchannel formed therein so that the microfluidic element is
disposed in communication with the microchannel to introduce the
microfluidic function into the microfluidic system.
16. The capping module of claim 15, further comprising a chamber
formed in the substrate, wherein the chamber is placed in fluid
communication with the microchannel when the capping module is
stacked on the microfluidic system.
17. The system of claim 15, wherein the microfluidic element
comprises a membrane.
18. The system of claim 15, wherein the microfluidic element
comprises a valve.
19. The system of claim 15, wherein the microfluidic element
comprises a pressure sensor.
20. The system of claim 15, wherein the microfluidic element
comprises a microfluidic pump.
Description
RELATED APPLICATIONS
[0001] The present application is a continuation of U.S. patent
application Ser. No. 10/329,018 filed Dec. 23, 2002, which claims
priority to U.S. Provisional Patent Application Ser. No. 60/409,489
filed Sep. 9, 2002, and U.S. Provisional Patent Application Ser.
No. 60/410,685, filed Sep. 13, 2002, the contents of which are
herein incorporated by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to a microfluidic system for
handling fluid samples on a microfluidic level. More particularly,
the present invention relates to a system and method for
implementing microfluidic functions in a microfluidic system.
BACKGROUND OF THE INVENTION
[0003] Microfluidic devices and systems provide improved methods of
performing chemical, biochemical and biological analysis and
synthesis. Microfluidic devices and systems allow for the
performance of multi-step, multi-species chemical operations in
chip-based micro chemical analysis systems. Chip-based microfluidic
systems generally comprise conventional `microfluidic` elements,
particularly capable of handling and analyzing chemical and
biological specimens. Typically, the term microfluidic in the art
refers to systems or devices having a network of processing nodes,
chambers and reservoirs connected by channels, in which the
channels have typical cross-sectional dimensions in the range
between about 1.0 .mu.m and about 500 .mu.m. In the art, channels
having these cross-sectional dimensions are referred to as
`microchannels`.
[0004] In the chemical, biomedical, bioscience and pharmaceutical
industries, it has become increasingly desirable to perform large
numbers of chemical operations, such as reactions, separations and
subsequent detection steps, in a highly parallel fashion. The high
throughput synthesis, screening and analysis of (bio)chemical
compounds, enables the economic discovery of new drugs and drug
candidates, and the implementation of sophisticated medical
diagnostic equipment. Of key importance for the improvement of the
chemical operations required in these applications are an increased
speed, enhanced reproducibility, decreased consumption of expensive
samples and reagents, and the reduction of waste materials.
[0005] In the fields of biotechnology, and especially cytology and
drug screening, there is a need for high throughput filtration of
particles. Examples of particles that require filtration are
various types of cells, such as blood platelets, white blood cells,
tumorous cells, embryonic cells and the like. These particles are
especially of interest in the field of cytology. Other particles
are (macro) molecular species such as proteins, enzymes and
poly-nucleotides. This family of particles is of particular
interest in the field of drug screening during the development of
new drugs.
SUMMARY OF THE INVENTION
[0006] The present invention provides a system and method for
integrating microfluidic components in a microfluidic system to
enable the microfluidic system to perform a selected microfluidic
function. The present invention utilizes a capping module including
a microfluidic element for performing a microfluidic function. The
capping module is stacked on a microfluidic substrate having
microfluidic plumbing to incorporate the microfluidic function into
the system.
[0007] According to one aspect, the invention provides a
microfiltration system in a microfluidic chip for separating a
substance, such as a compound, moving through a closed channel
system of capillary size into different components. The filtration
system of the invention provides a filtration module that can be
assembled at low cost while providing an accurate means of
filtering a large amount of compounds per unit of time. The
microfiltration system integrates conventional membrane filter
technology into a microfluidic system formed of glass, plastic or
other suitable material. The microfabricated filtration system may
comprise a sub-system designed to be inserted into a standard
microfluidic system to provide on-chip filtration. An illustrative
filtration system includes two flow paths separated by a membrane,
which separates a substance flowing through a first flow path by
size discrimination. Reservoirs are formed on either side of the
membrane in communication with the flow paths. A microfabricated
cap is affixed to the membrane to define the reservoir on the top
side of the membrane.
[0008] According to another aspect, an electromagnetic valve may be
incorporated into a microfluidic system using a capping structure
having electromagnetic valve components formed therein. The
electromagnetic valve components include a membrane for selectively
blocking flow through one or more communication ports in a
substrate and an actuator assembly for controlling the position of
the membrane.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] FIG. 1 illustrates a microfluidic system including a capping
structure for integrating a microfluidic function into the
microfluidic system.
[0010] FIG. 2 illustrates a diagnostic microfluidic chip suitable
for including a microfiltration system according to an illustrative
embodiment of the invention.
[0011] FIG. 3 is a perspective, cross-sectional view of the
microfiltration system in the chip of FIG. 2 according to an
illustrative embodiment of the invention.
[0012] FIG. 4 is a detailed view of the membrane on the
microfiltration system of FIG. 3.
[0013] FIG. 5 illustrates the microfabricated cap of the
microfiltration system of FIG. 3.
[0014] FIG. 6 is a top view of the microfiltration system of FIG.
3.
[0015] FIG. 7 is a top view of the diagnostic chip of FIG. 2 before
assembly of the microfiltration system.
[0016] FIG. 8 is a top view of the diagnostic chip of FIG. 2 after
assembly of the microfiltration system.
[0017] FIG. 9a is a top view of a two port direct microfiltration
system according to an alternate embodiment of the invention.
[0018] FIG. 9b is a perspective cross-sectional view of the
microfiltration system of FIG. 9a.
[0019] FIG. 10a is a top view of a three port direct
microfiltration system according to an alternate embodiment of the
invention.
[0020] FIG. 10b is a perspective cross-sectional view of the
microfiltration system of FIG. 10a, with the microfabricated cap
removed.
[0021] FIG. 11 illustrates an electromagnetic valve incorporated
into a microfluidic system according to an embodiment of the
invention.
DETAILED DESCRIPTION OF THE INVENTION
[0022] The present invention provides a microfabricated filtration
system for allowing on-chip filtration, purification or separation
of a sample. The microfabricated filtration system may be used in a
wide variety of applications, including, but not limited to blood
separation and filtration, microdialysis, microchemical analysis
and synthesis applications that require a filtration or dialysis
subsystem and other microfluidic application. The present invention
will be described below relative to an illustrative embodiment.
Those skilled in the art will appreciate that the present invention
may be implemented in a number of different applications and
embodiments and is not specifically limited in its application to
the particular embodiments depicted herein.
[0023] As used herein, the term "microfluidic" refers to a system
or device for handling, processing, ejecting and/or analyzing a
fluid sample including at least one channel having microscale
dimensions.
[0024] The terms "channel" and "flow channel" as used herein refers
to a pathway formed in or through a medium that allows for movement
of fluids, such as liquids and gases. The channel in the
microfluidic system preferably have cross-sectional dimensions in
the range between about 1.0 .mu.m and about 500 .mu.m, preferably
between about 25 .mu.m and about 250 .mu.m and most preferably
between about 50 .mu.m and about 150 .mu.m. One of ordinary skill
in the art will be able to determine an appropriate volume and
length of the flow channel. The ranges are intended to include the
above-recited values as upper or lower limits. The flow channel can
have any selected shape or arrangement, examples of which include a
linear or non-linear configuration and a U-shaped
configuration.
[0025] The term "microfluidic element" as used herein refers to a
component in a microfluidic system for performing a microfluidic
function, including, but not limited to: passive check valves,
active valves, pressure sensors, connecting channels, membrane
filtration units, threaded taps for external connecting tubes,
compression chambers, pumps, and others that may be known to those
of ordinary skill in the art.
[0026] The term "membrane" or "filter" as used herein refers to a
material of any suitable composition and size which may used to
separate or filter substances by size exclusion or other
measures.
[0027] The term "substrate" as used herein refers to a support
structure having channels formed therein for conveying a fluid.
[0028] The terms "cap" or "capping module" as used herein refer to
a structure, which is the same size as or smaller than a substrate,
having any selected size or shape and formed of any selected
material, and having a microfluidic element. The capping module is
configured to stack on or communicate with the substrate to fully
or partially complete a fluid path.
[0029] The term "substance" as used herein refers to any material
used in a microfluidic process, including, but not limited to
chemical compounds, molecules, viruses, cells, particles, beads,
buffers, or any other material used in a microfluidic process.
[0030] The term "microfluidic function" as used herein refers to
any operation, function or process performed or expressed on a
fluid or sample in a microfluidic system, including, but not
limited to: filtration, dialysis, pumping, fluid flow regulation,
controlling fluid flow and the like.
[0031] The term "port" refers to a structure for providing fluid
communication between two elements.
[0032] As used herein, "pump" refers to a device suitable for
intaking and discharging fluids and can have different sizes,
including microscale dimensions, herein referred to as
"micropump."
[0033] The present invention allows implementation of different
microfluidic functions into a microfluidic chip using a capping
module having a microfluidic element for performing a microfluidic
function. As shown in FIG. 1, a microfluidic chip 10 suitable for
implementing an embodiment of the invention comprises a substrate
11 having one or more flow channels 3, illustrated as a
microchannel, disposed therein. The flow channels transport fluid
through the microfluidic system 10 for processing, handling, and/or
performing any suitable operation on a liquid sample. The
microfluidic system 10 may comprise any suitable number of flow
channels 3 for transporting fluids through the microfluidic system
10.
[0034] As shown in FIG. 1, the flow channel 3 is formed in a
substrate 11, and may connect to the surface of the substrate via
one or more communication ports 13a and 13b. A capping module 15
including a microfluidic element 18, such as a filter, one or more
valves, pressure sensors or other component for performing a
microfluidic function, is placed over the substrate 11 to form a
closed fluid path. According to an alternate embodiment, the
capping module may include a connector channel for re-routing fluid
flow through the microchannel around another structure. The
illustrative substrate 11 includes two communication ports 13a,
13b, each connecting unconnected segments 3a, 3b of the flow
channel 3 to the substrate surface, though one skilled in the art
will recognize that variations may be made in the size, number and
configuration of the communication ports and flow channels.
[0035] The illustrative capping module 15 may include connector
ports for interfacing with the communication ports of the
substrate, and/or a chamber 12 or channel to provide a fluidic path
between the first connector port and the second connector port. One
skilled in the art will recognize that the capping module may have
alternate configurations and is not limited to the embodiment shown
in FIG. 1.
[0036] Using the capping module 15, microfluidic functions, such as
filtration, dialysis, pumping, flow control and so on, may be
integrated into the microfluidic system 10 without requiring
significant modification of the substrate 11. A substrate including
any number and arrangement of conduits or channels 3 for conveying
fluids can be transformed into a functional fluidic circuit by
selecting and placing one or more capping modules 15 with a
functional microfluidic element 18 on the substrate, i.e. chip.
According to an illustrative embodiment, the same automated "pick
and place" surface mount equipment technology used to make
integrated circuits may be used to form fluidic circuits on a
substrate having microchannels using various capping structures.
Suitable pick and place equipment is manufactured by Manncorp, Inc.
(Huntingdon Valley, Pa.), among others.
[0037] To fabricate a fluidic circuit, the channels 3 in the
substrate 11 may be manufactured by chip microfabrication. The
channels or plumbing may be fabricated by etching half-channels in
a first substrate, followed by bonding and/or lamination of a
second substrate to enclose the half-channels, forming a
microchannel. The substrate may be formed of one or more layers
containing etched channels if more complex fluidic networks are
required. The communication ports may then be fabricated in the
substrate to connect the microchannel to an exterior surface of the
substrate. Suitable techniques for fabricating the communication
ports include drilling, laser etching, powder blasting or other
techniques known in the art. After the fabrication of the substrate
and communication ports, a capping module having a desired
functionality is bonded to the substrate to form a microfluidic
component in the larger microfluidic circuit.
[0038] A variety of capping module number and sizes may be bonded
to the substrate to impart various microfluidic functions to form a
microfluidic system. The capping modules may be removable and
replaceable so that a substrate may be re-used.
[0039] According to the illustrative embodiment, the capping module
has a cross-sectional dimension of between about 1 millimeter and
about 5 centimeters, though those skilled in the art will recognize
that the invention is not limited to this range. The capping module
may be formed of any suitable material, including, but not limited
to plastic, glass, silicon and other materials known in the
art.
[0040] FIG. 2 illustrates the architecture of an illustrative
microfluidic diagnostic chip that may be fabricated according to
the teachings of the invention. The diagnostic chip 20 may include
one or more microfluidic components, alone or in combination,
configured to facilitate processing of a sample. For example, as
shown, the diagnostic chip 20 includes a microfiltration system 100
for separating substances in solution, such as separating selected
particles from cells or other particles in a suspension. The
diagnostic chip 20 may further include one or more reservoirs 90
for storing and supplying sample, reagent or other compounds to the
system, as well as one or more waste reservoirs 91 for collecting
sample waste. The diagnostic chip may further include one or more
aliquoting, mixing and incubation components, such as an on-chip
sample dilution system, for processing a sample, such as performing
a mixture of a specific amount of sample and reagent. For example,
the illustrative system includes a mixing component 60 and an
incubation region 61. The chip may also include a detector 70 for
analyzing a filtered product from the microfiltration system 100.
The detector 70 may utilize any suitable detection modality,
including, but not limited to fluorescence, electrochemical
analysis, dielectrophoresis, and surface plasma resonance (SPR),
radio-frequency, thermal analysis and combinations thereof. The
chip 10 may employ valves for selectively controlling the flow of
fluid through the channels and one or more drive units, located on
or off the chip, for driving the movement of fluid through the
channels 3 of the chip. One skilled in the art will recognize that
the microfluidic system is not limited to the diagnostic chip of
FIG. 2 and that variations in the configuration, position, number
and combination of the various microfluidic components may be made
in accordance with the present invention.
[0041] The filtration system 100 of the present invention
integrates conventional membrane filter technology into a
microfluidic chip using a capping module. The filtration system can
be inserted into an existing microfluidic chip to enable filtration
of particles, cells or other substances in suspension without
requiring significant or expensive modification of the chip
structure.
[0042] FIGS. 3, 4 and 6 illustrate a microfabricated filtration
subsystem 100 suitable for implementation in the microfluidic
system of FIG. 2 according to one embodiment of the invention. FIG.
5 illustrates the capping module 15 used to fabricate the
filtration system 100 according to one embodiment of the invention.
The filtration subsystem is utilized to separate a substance, such
as a sample comprising a mixture of particles and fluid, through a
membrane 110 and subsequently collect the separated components.
According to an illustrative embodiment, the filtration subsystem
is used to separate blood cells from plasma, though one skilled in
the art will recognize that other applications are included in the
invention. According to other applications, the filtration system
may be used to separate viruses from cells, beads from cells,
chemical compounds, molecules or other substances that a membrane
may be used to separate. As shown the filtration subsystem 100 is
formed directly on the microfluidic chip to add filtration
capability to the chip without requiring significant modification
or expense.
[0043] The filtration subsystem 100 utilizes a conventional
membrane filter 110 separating two flow paths in the substrate 11
to provide small volume controllable filtration of a sample. The
illustrative filtration system is a four-port transverse filter,
which includes a first fluid flow path 120 for supplying a
substance to the filtration system, such as a mixture of particles
and fluid, and a second fluid flow path 130 for receiving and
conveying a filtered product (i.e., a filtrate) from the filtration
system. The first fluid flow path 120 includes a first
communication port, illustrated as a first inlet channel 121 that
intersects the filtration system at a first inlet 121a. The first
fluid flow path 120 includes a second communication port,
illustrated as a first outlet channel 122 including an outlet 122a
from the filtration chamber for receiving and conveying a retentate
of the substance from the filtration system. The second fluid flow
path includes an inlet channel 131 intersecting a filtrate chamber
below the membrane 110 at a second inlet and a second outlet
channel 132 for transferring the filtered product from the
filtration system. The second fluid flow path 130 may include a
carrier fluid for conveying the filtered product. A flow source
drives the flow of the mixture through the filtration system to
effect separation of the components through the membrane. The flow
source may comprise an off-chip syringe pump, a microfabricated
peristaltic pump, a microfabricated syringe, or any suitable flow
source known in the art, such as those described in U.S.
Provisional Patent Application Ser. No. 60/391,868 entitled
"Microfluidic System and Components", (Attorney Docket Number
CVZ-019-2), the contents of which are herein incorporated by
reference.
[0044] The illustrative microfabricated filtration system 100 has a
relatively small footprint (less than about one mm.sup.2),
resulting in a compact structure, low cost and relatively simple
fabrication. The particle separator further provides relatively low
strain rates with reduced or no blockage. The amount of fluid
retained can be significant, if desired, and the design is scalable
and repeatable for additional parsing steps, if desired.
[0045] The filtration subsystem of the present invention may be
formed by providing a microfluidic chip including an intersection
101 of the two flow channels 120, 130. The assembly process
integrates simple batch fabricated components, and is relatively
simple and low cost at high volume. According to an illustrative
embodiment, the chip forms a recess 140 in communication with the
second flow channel 130 at the intersection 101. The first flow
channel 120 is initially separated from and divided by the recess
140. A suitable membrane 110 is affixed to the microfluidic chip,
using an appropriate adhesive or other suitable fastening
mechanism, to cover the recess, thereby defining a reservoir below
the membrane for receiving the filtered product and transmitting
the filter product through the second flow channel 130. The
membrane may comprise any suitable filtering membrane known in the
art.
[0046] The illustrative microfabricated capping module 15, shown in
FIG. 4, is affixed above the membrane 110 to define a filtration
chamber 161 in communication with the first flow channel 120. The
cap 15 may be affixed using an appropriate adhesive or other
suitable fastening mechanism. The illustrative capping module 15
includes an inlet 162 and an outlet 163 in communication with the
filtration chamber to connect the first flow channel 120 with the
filtration chamber 161 and enable flow of a composition to be
filtered through the filtration chamber over the membrane.
Alternatively, the membrane 110 is affixed directly to the capping
module 15 and the capping module is affixed to the substrate to
integrate the filtration system onto the substrate. One skilled in
the art will recognize that the capping module is not limited to
the illustrative embodiment and that variations may be made in
accordance with the teachings of the invention.
[0047] FIG. 7 illustrates the microfluidic system 10 including
channels 3 prior formed therein prior to assembly of the capping
module 15 including the membrane 110. FIG. 8 is a top view of the
capped microfluidic system 10 incorporating filtering
capability.
[0048] The composition to be filtered is introduced to the
filtration subsystem from the inlet channel and passes into the
filtration chamber and over the membrane 110. The components of the
substance are fractionated by the membrane 110, with the smaller
components, such as plasma, passing through the membrane, into the
reservoir 140 and through the second flow channel 130. The
remaining portion, such as blood cells, passes through the
filtration chamber to the outlet of the first flow channel 120.
[0049] According to the illustrative embodiment, the substrate of
the microfluidic chip may be formed of glass, plastic, silicon,
quartz, ceramics or any other suitable material. In a microfluidic
chip manufactured from glass, the chip may comprise two layers: the
chip and the cap affixed to the chip to define the filtration
subsystem. In a microfluidic chip formed of plastic, the components
may be stamped into the plastic substrate.
[0050] According to an alternate embodiment, shown in FIGS. 9a and
9b, the microfiltration subsystem may comprise a two-port direct
filter 180 comprising a membrane 110 inserted into a fluid flow
path 181. As shown, the two-port direct filter 181 comprises a
fluid flow path 181 formed in a microfluidic substrate, which is
divided into two sections 181a, 181b. The second section 181b
defines a recess 182 and the membrane 110 is adhered over the
recess to define a filtrate chamber for receiving a filtered
product. A microfabricated cap 15 including a recess 186 defining a
filtration chamber is attached to substrate above the membrane to
connect the flow path 181. The substance to be filtered is conveyed
through the fluid flow path 181 into the filtration chamber 186 and
passes through the membrane 110. The membrane 110 separates the
substance by trapping larger molecules and the filtered product,
comprising the remaining molecules, passes through the membrane
along the fluid flow path 181 into the recess 182 and out of the
microfiltration system for further analysis, processing collection,
etc.
[0051] According to yet another embodiment, shown in FIGS. 10a and
10b, the microfiltration system may comprise a three port direct
filter 190. The three port direct filter 190 includes two inlet
flow channels 191, 192 for inputting two samples to a filtration
chamber 195 and a single outlet channel 193 for conveying a
filtered product from the filter 190. The three-port direct filter
includes a microfabricated cap 15 defining the filtration chamber
and a membrane 110 separating the filtration chamber from the
outlet channel 193. In operation, two samples may be provided
through the inlet channels 191, 192. The samples mix together in
the filtration chamber 195 and the sample mixture is filtered
through the membrane, which separates the components of the sample
mixture. The filtered product that passes through the membrane is
conveyed through the outlet channel for further processing,
analysis, collection etc.
[0052] One skilled in the art of membrane based separations will
recognize that the filtration system described here can be used to
implement on-chip separations of all types for which membranes may
be found, including separating molecules by size or beads from
molecules or small particles from large particles or viruses from
cells or other separations known to those skilled in the art.
[0053] According to another embodiment of the invention, the
capping module 15 may be used to incorporate an electromagnetic
valve into a microfluidic system. An example of an electromagnetic
valve component housed in a capping structure for implementation in
a microfluidic system according to the teachings of the invention
is shown in FIG. 11. As shown, the electromagnetic module 150
comprises a cap 15 defining an interior chamber 151, a membrane 154
for selectively blocking flow through one or both of the
communication ports in the substrate and an actuator assembly 160
for deflecting the membrane 154. According to the illustrative
embodiment, the actuator assembly comprises a coil 162 and a magnet
164. One skilled in the art will recognize that other suitable
means for deflecting the membrane may be used, including
piezoelectric actuators.
[0054] The electromagnetic capping module 110 may be stacked on the
substrate 11 such that the membrane, when deflected, blocks one or
more of the communication ports 13a and 13b. The electromagnetic
capping module 110 thus integrates a valve for selectively blocking
flow through the channel 3 into the microfluidic flow path. As
described above, the electromagnetic capping module may be placed
on the substrate using automated "pick and place" equipment or
through any suitable means known in the art.
[0055] One skilled in the art will recognize that the capping
module is not limited to the illustrative embodiment and that other
elements may be implemented to add other microfluidic functions, in
addition to or in place of, filtration and flow control.
[0056] The microfiltration system of the present invention
advantageously combines the power and scope of conventional
membrane technology with the small volume dynamic flow control
inherent in microfabricated/microstruct- ure microfluidic systems.
The present invention provides cost effective mixing of any
suitable polymer membrane with a microfluidic network. The
microfiltration system is simple and inexpensive to add to a
microfluidic system, as the incremental cost of assembling the
microfiltration system in a microfluidic chip is relatively low
above the cost of the microfluidic system itself A microfluidic
system according to the present invention may comprise one or more
of the above-described components, alone or in combination with
other components.
[0057] The present invention has been described relative to an
illustrative embodiment. Since certain changes may be made in the
above constructions without departing from the scope of the
invention, it is intended that all matter contained in the above
description or shown in the accompanying drawings be interpreted as
illustrative and not in a limiting sense.
[0058] It is also to be understood that the following claims are to
cover all generic and specific features of the invention described
herein, and all statements of the scope of the invention which, as
a matter of language, might be said to fall therebetween.
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