Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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MICRO-CHANNEL DESIGN FEATURES THAT
FACILITATE CENTRIPETAL FLUID TRANSFER
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] The present application claims a priority benefit from earlier filed:
U.S.
Provisional Patent Application No. 60/399,548, filed July 30, 2002; U.S.
Provisional
Patent Application No. 60/398,851, filed July 26, 2002; and U.S. Patent
Applications
Nos. 10/336,274 10/336,706, and 10/336,330, all filed January 3, 2003; all of
which are
incorporated herein in their entireties by reference.
FIELD
[0002] The present application relates to microfluidic devices, systems that
include
such devices, and methods that use such devices and systems. More
particularly, the
present application relates to devices that manipulate, process, or otherwise
alter micro-
sized amounts of fluids and fluid samples.
BACKGROUND
[0003] Microfiuidic devices are used for manipulating fluid samples. There
continues
to exist a demand for microfluidic devices, methods of using them, and systems
incorporating them for processing samples that are fast, reliable, consumable,
and can be
used to process large number of samples simultaneously.
SUMMARY
[0004] According to various embodiments, a microffuidic device is provided
having a
flow channel and including an excess fluid capture reservoir. The device can
provide a
metered quantity of sample for processing and capture all excess sample.
[0005] According to various embodiments, a microfluidic device is provided
having a
substrate having a first surface, an opposite second surface, and a thickness,
an input port
formed in at least one of the first and second surfaces, and a manifold formed
in the
substrate and in fluid communication with the input port, the manifold
including a feed
channel that extends in a first direction, and a plurality of branch channels
each branching
off the feed channel and each terminating at a closed end. The branch channels
can be
parallel to one another. The substrate can also include a plurality of
respective chambers,
at least one chamber formed in the substrate adjacent the closed end of each
branch
channel.
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[0006] According to various embodiments, a sample processing system is
provided
having a microfiuidic device and a processing apparatus. The microiluidic
device includes
a substrate having a first surface, an opposite second surface, and a
thickness, an input
port formed in at least one of the first and second surfaces, and a manifold.
The manifold
can be formed in the substrate and in fluid communication with the input port,
and can
include a feed channel that extends in a first direction, and a plurality of
parallel branch
channels branching off the feed channel. The branch channels can be parallel
to one
another. The processing apparatus can include a rotatable platen having an
axis of
rotation, a holder capable of holding a microfluidic device on or in the
platen and being
disposed off center with respect to the axis of rotation, and a drive unit to
rotate the
platen about the axis of rotation.
[0007] According to various embodiments, a sample processing system is
provided
having a microfiuidic device and a processing apparatus. The microfiuidic
device can
include a substrate having a first substantially rectangular surface, a second
substantially
rectangular surface opposite the first surface, a thickness, a length, a
width, and a plurality
of geometrically parallel processing pathways arranged parallel to either the
length or the
width of the substrate. The processing apparatus can include a rotatable
platen having an
axis of rotation, and a holder capable of holding the microfiuidic device on
or in the platen
and disposed off center with respect to the axis of rotation. The holder can
be capable of
holding the microfluidic device in or on the platen such that any radius of
the platen that is
parallel to the length or the width of the microfiuidic device does not
intersect the other of
the width or the length, respectively, of the microfluidic device.
[0008] According to various embodiments, a method of distributing a liquid
sample
into a plurality of branch channels in a microfiuidic device is provided that
can include
providing a microfluidic device, izitroducing a liquid sample through an input
port and into
a feed channel of the device, and centrifugally spinning the microfiuidic
device to force
fluid from the feed channel into the branch channels. The microfiuidic device
can include a
substrate, an input port, and a manifold, wherein the substrate includes a
first surface, an
opposite second surface, and a thickness, the input port is formed in at least
one of the
first and second surfaces, and the manifold is formed in the substrate in
fluid
communication with the input port. The manifold can include the feed channel
that
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extends in a first direction, and a plurality of branch channels each
branching off the feed
channel normal to the feed channel. The branch channels can be parallel to one
another.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] Fig. 1 is a top view of a microfiuidic device having a fluid capture
appendix;
[00010] Fig. 2 is a top view of a microfluidic device having a manifold having
a feed
channel and a plurality of parallel branch channels;
[00011] Fig. 3 is a top view of a microfiuidic device having a flow sputter;
[00012] Fig. 4 is a side view of a microfiuidic device having a flow sputter
in the depth
profile of a substrate;
[00013] Figs. Sa-Sd are cross-sectional views of microfiuidic channels having
various
profiles in the substrate;
[00014] Fig. 6a is a top view of a microfiuidic device depicting a rectangular
substrate
oriented to allow fluid movement across the length of the substrate;
[00015] Fig. 6b is a top view of a microffuidic device depicting a rectangular
substrate
oriented to allow fluid movement across the width of the rectangular
substrate;
(00016] Fig. 6c is a top view of a platen holding two microfiuidic devices
each including a
rectangular substrate;
[00017] Fig. 7a is a top view of a microfiuidic device having teardrop-shaped
input ports
oriented such that, when the microfiuidic device is held on and spun by a
rotatable platen, the
narrow end of the teardrop-shaped input ports is radially further away from an
axis of rotation
than the circular end of the teardrop-shaped input port;
[00018] Fig. 7b is an enlarged portion of Fig. 7a taken along dashed line 7b,
shown in Fig.
7a; and
[00019] Figs. 8 is a diagram of a microfluidic device having a plurality of
input ports
capable of distributing a fluid sample to a respective plurality of flow
distributors, each flow
distribution respectively in fluid communication with a plurality of pathways.
DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS
[00020] According to various embodiments, a microfluidic device is provided
having a
flow channel and including an excess fluid capture reservoir. The device can
provide a
metered quantity of sample for processing and capture all excess sample.
[00021] Fig. 1 is a top view of a microfluidic device 140 that can be used,
for example, to
capture an excess fluid sample which can be retained after sample processing,
for example,
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after PCR amplification. Microfluidic device 140 includes a substrate 142
having an input port
106 and an input charnel 144. Input channel 144 connects to a feed channel 150
that is
divided into two parallel branch channels 146 and 148 of unequal volume.
Parallel branch
channel 148 can be used as an excess fluid capture reservoir appendix. Input
channel 144 is
upstream of parallel branch channels 146 and 148. Upstream of input channel
144 can be an
input port 106 as shown, or a chamber, well, or opening. While the parallel
branch channel
148 is designed as an appendix and is not in any fi~rther fluid communication
with any other
chambers, the parallel branch channel 146 can be in fluid communication with
other chambers,
wells, or openings further downstream, or can be made to be in fluid
communication as by
valuing.
[00022] According to various embodiments, a PCR reaction can be performed, for
example, in a 5 pL volume, wherein a 2 pL volume can be required for the
sequencing
reaction, and a remaining 3 pL volume can be used for diagnostics. A user can
analyze
this excess diagnostic material on an agarose gel to verify that fragments are
being
properly amplified. To enable analysis, parallel branch channel 148 can be
used as a fluid
capture appendix. Branch channel 146 can contain 2 pL of sample 154 while an
excess 3
pL of sample 156 can be contained in parallel branch channel 148. In various
embodiments, a valve can be opened after distribution of the sample into the
parallel
branch channels, and the 2 pL sample 154 can flow to a subsequent reaction
chamber, for
example, an EXO-SAP chamber, while the excess sample 156 remains in branch
channel
148. According to various embodiments, the excess sample 156 can be accessed
by
piercing a cover 152 of the device with a needle, syringe, or pipette, and
carefully
extracting a desired amount of sample 156 from branch channel 148.
[00023] According to various embodiments, a microfiuidic device is provided
having a
substrate having a first surface, an opposite second surface, and a thickness,
an input port
formed in at least one of the first and second surfaces, and a manifold formed
in the
substrate and in fluid communication with the input port. The manifold can
include a feed
channel that extends in a first direction, and a plurality of branch channels
each branching
off the feed channel and each terminating at a closed end. The branch channels
can be
parallel to one another. The substrate can also include a plurality of
respective chambers,
at least one chamber formed in the substrate adjacent the closed end of each
branch
channel. Each of the plurality of branch channels can extend in a direction
normal to the
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feed channel. Each of the plurality of branch channels can be in interruptible
fluid
communication with a respective pathway having at least one processing
chamber. A
valve can be provided between each of the branch channels and its respective
at least one
processing chamber. Each of the plurality of branch channels can have a valve.
The
manifold can contain a first volume of fluid, about equal to the collective
volume of the
plurality of branch channel volumes. According to various embodiments, each of
the
plurality of branch channels in the microfluidic device extends in a direction
that can be
parallel to and/or normal to the first surface of the substrate in the
microfluidic device.
[00024] According to various embodiments, each of the plurality of branch
channels has
a volume. The collective volume of the plurality of branch channels in the
microfluidic
device can be from about 5 pl to about 100 p.l, for example, about 50 pl. The
volume of
each parallel branch channel can be from about 0.05 ~.1 to about 5 pl, for
example, 0.5 p.l,
1 p,l, or 2 ~ 1.
[00025] According to various embodiments, the input port of the, microfluidic
device can
be teardrop-shaped, having a wide end and a narrow end, wherein the narrow end
is in
fluid communication with the feed channel.
[00026] Fig. 2 is a top view of a microfluidic device 100. Microfluidic device
100 can
be formed in a substrate 108. Microfluidic device 100 can include an input
port 106 in
fluid communication with an input channel 104 connected to a feed channel 110.
A
plurality of parallel branch channels 102 can connect to feed channel 110.
Microfluidic
device 100 can in this configuration be used as a flow distributor.
Microfluidic device 100
can be used to split a single fluid sample into a plurality of sub-portions.
Similar
microfluidic devices but used to divide a sample into only two portions are
referred to
herein as flow sputters.
[00027] In operation, microfluidic device 100 can be placed on a rotatable
platen (not
shown) and the platen can be spun. Substrate 108 can be oriented in a holder
in, on or for
the platen such that input channel 104 can be radially closer to the center of
the platen
than the plurality of parallel branch channels. According to various
embodiments, input
channel 104 can be disposed in substrate 108 such that input channel 104
connects to feed
channel 110 at a radially measured point along feed channel 110 closest to the
center of
the platen and centrifugation provides a plurality of aliquots or sample
portions 112.
According to various embodiments, fluid distributors for splitting the fluid
sample from
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one sample into 2 or more samples or aliquots, can be formed, for example, for
splitting a
sample into 2, 3, 6, 12, 24, 48, 96, 192, or 384 samples or aliquots.
[00028] Parallel branch channels 102 can be used to obtain equal volumes of
fluids in
as many portions or aliquots 112 as desired. Parallel branch channels 102 can
be in fluid
communication with processing chambers (not shown) forming individual pathways
for
further processing of each aliquot 112. The pathways can be used to perform a
single
reaction or process, for example, forward sequencing, or can perform multiple
same or
multiple distinct reactions or processes, for example, PCR, on an aliquot.
Reagents '
needed to perform a certain reaction or process in the processing chamber of a
pathway
can be loaded in the respective processing chamber at the time of manufacture
of the
microfluidic device 100, or can be loaded at the time of use.
[00029] According to various embodiments, parallel branch channels 102 can
have
reagents disposed therein such that a reaction can take place in parallel
branch channels
102. Reagents can be disposed in the processing chambers using any methods
known in
the art. For example, reagents can be sprayed and dried, delivered using a
diluent, injected
using a capillary, a pipette, andlor a robotic pipette, or otherwise disposed
in the
processing chambers or channels.
[00030] According to various embodiments, input channel 104 can connect to
feed
channel 110 at any point on feed channel 110 that opposes parallel branch
channels 102.
The connection can be, for example, at a midpoint of feed channel 110 or
proximate to an
end of feed channel 110. According to various embodiments, feed channel 110
can be an
input port. According to various embodiments, parallel branch channels 102 do
not
connect with feed channel 110 at a right angle.
[00031] According to various embodiments, fluid communication downstream of
parallel branch channels 102 can be interruptible by using a plurality of
respective valves
(not shown). According to various embodiments, each parallel branch channel
102 can
have a respective valve in fluid communication with the parallel branch
channel 102.
Microfluidic device 100 can be spun on a platen to deliver a fluid sample from
input port
106 to each parallel branch channel 102 before valves in fluid communication
with each
parallel branch channel 102 are manipulated. According to various embodiments,
a valve
does not have to be in fluid communication with one or more of parallel branch
channels
102. According to various embodiments, a fluid sample can be manipulated
through feed
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channel 110 and can fill a first parallel branch channel 102 until overflow
from that
parallel branch channel 102 flows into the next, adjacent parallel branch
channel.
[00032] Fig. 3 is a top view of a microfluidic device 120 that includes a
substrate 128
and a cover layer 121. Input channel 122 under cover layer 121 connects to a
manifold
including feed channel 126 and a plurality of parallel branch channels 124 in
fluid
communication with the feed channel 126, all also under cover layer 121. Input
channel
122 can connect to feed channel 126 proximate to a mid-point of feed channel
126.
[00033] Figs. 1-3 depict flow sputters formed in a microfluidic device in a
planar
format, for example, either in a first surface or a second surface of the
substrate. This
arrangement is in the horizontal plane and is one possible embodiment for
splitting a fluid
sample. According to various embodiments, the fluid sample can be split in a
vertical
plane of the substrate.
[00034] According to various embodiments, a flow distributor can be formed
within a
thickness of a substrate. According to various embodiments, the flow splitter
implemented in the vertical plane can have a closed-end branch channel, an
open-end
branch channel, or a plurality of open-end and/or close-end branch channels,
or a
combination thereof. A closed-end branch channel can be an appendix such as a
fluid
capture appendix.
[00035] According to various embodiments, a flow distributor can be right
justified
or left justified with respect to its placement in a holder in a rotatable
platen in a direction
toward a central axis of rotation of the platen. A right justified flow
distributor has an
input channel connected to a right-end of the feed channel. A left justified
flow distributor
has an input channel connected to a left-end of the feed channel. A flow
distributor can be
center justified, having an input channel connected to a proximate center
along the length
of the feed channel.
[00036] Fig. 4 is a side-perspective view of a microfluidic device 160
according to
various embodiments. An input channel 172 is in fluid communication with a
manifold
including feed channel 170. Feed channel 170 is in fluid communication with
parallel
branch channels 168 and 174 formed in a substrate 162. The microfluidic device
further
includes a first cover 164 and a second cover 166, for example, made of
plastic or metal
filin or foil. In the embodiment shown, parallel branch channels 168 and 174
are formed in
the depth dimension of substrate 162. A volume of sample fluid can be retained
in parallel
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branch channel 168 of microfiuidic device 160. According to various
embodiments, the
fluid can be transferred to a subsequent channel or chambers after opening a
valve (not
shown), or stored in parallel branch channel 168 for future analysis. When the
fluid is
stored, parallel branch channel 168 can be used as an appendix, reservoir, or
other device
for excess fluid capture. The arrangement of chambers, valves, channels, and
vial as
described and shown with reference to Fig. 4 is referred to herein as a
vertical splitter.
[00037] According to various embodiments, microfiuidic devices, for example,
microfiuidic devices 100, 120, 140; and 160 described in the various figure
herein, can be
formed in a rectangular substrate. An input port of the microfluidic device
can be a
teardrop-shaped chamber. According to various embodiments, the microfiuidic
device can
be held in or on a platen and rotated around a central axis of rotation of the
platen. A
rotational force necessary to spin the platen including the microfiuidic
device can be
sufficient to communicate a fluid from an input port of the microfiuidic
device into a flow
distributor, into a flow restrictor, and/or through a valve. A volume of
sample fluid
captured in an appendix of the microfiuidic device can be greater, the same,
or less than
the volume of fluid in a parallel branch channel.
[00038] Figs. Sa-Sd are cross-sectional views of various channel profiles that
can be used in
microffuidic devices according to various embodiments. In Fig. Sa, channel 242
is formed with
a rectangular cross-sectional area in a substrate 240. The cross-sectional
area has an aspect
ratio, that is, a width/depth ratio, of greater than one. In Fig. Sb, channel
246 is formed with a
semi-oval cross-sectional area in a substrate 244. The cross-sectional area
has an aspect ratio,
that is, a width/depth ratio, of greater than one. In Fig. Sc, a thin and
narrow channel 250 is
formed in a substrate 248, wherein the cross-sectional area has an aspect
ratio, that is, a
width/depth ratio, of less than one. In Fig. Sd, a channel 254 is formed with
a trapezoidal
cross-sectional area in a substrate 252 and generally has an aspect ratio of
les than one. These
and other cross-sectional designs can be used as channels, for example, flow-
restricting
channels, and can be preformed or formed during a valve-opening operation
according to
various embodiments.
[00039] The dimensional characteristics of an exemplary straight channel flow
restrictor
cross-section can be, for example, about 0.2 mm by about 0.2 mm. The width of
such a
channel can be from about 0.05 mm to about 0.5 mm, for example, about 0.2 mm.
The height
of such a channel can be from about 0.05 mm to about 0.5 mm, for example,
about 0.2 mm
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The length of such a channel can be, for example, from about 0.1 mm to about
10 cm, for
example, about 5 mm. A flow restrictor can be used in conjunction with a
larger chamber
having a minimum dimension greater than approximately 0.50 mm, and can serve
to retain
particles in a chamber, for example, P-10 beads available from BioRad, size-
exclusion ion-
exchange beads, particulates, size-exclusion chromatography beads, other
particles known to
those skilled in the art, or a combination thereof. The flow restrictor can be
located
downstream of the chamber holding the particles. Downstream means the flow
restrictor is
located at a greater distance away from the axis of rotation when the device
is operably held
on a rotatable platen, than the chamber. When subjected to a centripetal
force, the fluid sample
and the particulates in the chamber can move toward the flow restrictor where
the particulates
can be retained while the fluids can pass into an adjacent channel or chamber.
[00040] According to various embodiments and as described above, dimensions
ofthe flow
restrictor are not limited to square cross-sections. Other shapes can be
successfully
implemented. For example, a rectangular flow-restricting channel having a
cross-section with
about a 0.10 mm depth and about a 0.30 mm width can be formed in a substrate
to retain gel
filtration media such as P-10 beads available from BioRad.
[00041] Fig. 6a is a top view of a microffuidic device 200 having a plurality
of input
ports 202 leading to a plurality of respective processing pathways, one of
which is shown
as 203. The exemplary processing pathway 203 can be in fluid communication
with an
exemplary output port 205. The flow arrow shown depicts a direction of fluid
movement
from input port 202 to output port 205. Input port 202 can be teardrop-shaped
having a
narrower-end 204 oriented in the same direction as the direction of fluid
movement. The
processing pathway 203 can be disposed across a length of the microfluidic
device,
wherein the length of the microfluidic device is greater than a width of the
microfluidic
device.
[00042] Fig. 6b is a top view a microfluidic device 210 having a plurality of
input ports
212 leading to a plurality of respective processing pathways, one of which is
shown as
213. The exemplary processing pathway 213 can be in fluid communication with
an
exemplary output port 215. A flow arrow depicts a direction of fluid movement
from
input port 212 to output port 215. The processing pathway 213 can be disposed
across a
width of the rnicrofluidic device wherein a length of the microfluidic device
is greater than
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the width of the microffuidic device. An alignment pinhole 214 and an
alignment notch
216 can be provided in the microfluidic device 210.
[00043] Fig. 6c is a top view of a sample processing system that includes a
rotatable
platen 220 having a central axis of rotation 222, and microfluidic devices 224
and 226.
Microfluidic device 224 can be oriented on platen 220 such that input ports
225 can be
radially closer to axis of rotation 222 than the respective processing
pathways 221.
Similarly, microfluidic device 226 can be oriented on platen 220 such that
input ports 227
can be radially closer to axis of rotation 222 than the respective processing
pathways 228.
Microfluidic devices 224, 226 can be held to platen 220 using a holder (not
shown).
Orientation for placement of microfluidic device 224, 226 can be assisted by
one or more
alignment pinholes 229, alignment pins (not shown), alignment notches,
alignment
recesses, or the like, in or included with the holder.
[00044] According to various embodiments, a sample processing system having a
microfluidic device formed in a substrate and a holder to secure the
microfluidic device
can include at least one alignment pinhole formed in the substrate and at
least one
alignment pin in the holder. The at least one alignment pinhole can be
complementary to
the at least one alignment pin. The alignment pinhole can extend from a first
surface of the
substrate to an opposing second surface, thus forming a hole through the
substrate. T'he
alignment pinhole can partially extend through the first surface, without
extending
through the substrate to the second surface. Alignment can be by a notch on an
edge of
the substrate, for example, a semi-circular notch, a triangular notch, or a
square notch. In
various embodiments, at least one alignment pin complementary to the at least
one
alignment pinhole or notch, can be disposed in a holder to hold the
microfluidic device to
a rotatable platen.
[00045] According to various embodiments, a sample processing system is
provided
having a microfluidic device and a processing apparatus. The microfluidic
device includes
a substrate having a first surface, an opposite second surface, and a
thickness, an input
port formed in at least one of the first and second surfaces, and a manifold.
The manifold
can be formed ir1 the substrate and in fluid communication with the input
port. The
manifold can include a feed channel that extends in a first direction, and a
plurality of
branch channels branching off the feed channel. The branch channels can be
parallel to
one another and can be normal to the feed channel. The processing apparatus
can include
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a rotatable platen having an axis of rotation, a holder capable of holding a
microfluidic
device on or in the platen and being disposed off center with respect to the
axis of
rotation, and a drive wut to rotate the platen about the axis of rotation. The
microfluidic
device can be held by the holder such that any radius of the platen which is
parallel to the
length or the width of the microffuidic device does not intercept the other of
the width or
the length, respectively, of the microfluidic device. The microffuidic device
can include a
plurality of input ports formed in the substrate, and a respective plurality
of manifolds in
fluid communication with the plurality of input ports.
[00046] According to various embodiments, a method of distributing a liquid
sample
into a plurality of branch channels in a microfluidic device is provided that
includes
providing a microfluidic device, introducing a liquid sample through an input
port and into
a feed channel of the microfluidic device, and centrifugally spinning the
microfluidic
device to force fluid from the feed channel into one or more of a plurality of
branch channels
of the microfluidic device. The microffuidic device can be part of a sample
processing system
that includes a rotatable platen with the microfluidic device held therein or
thereon.
[00047] The holder for holding a microfluidic device in or on a platen, as
described
herein, can be formed using various methods and/or apparatuses. The holder can
include a
recess in the platen in which a microffuidic device can be placed and
recessed. The holder
can include pin and hole combinations, pin and notch combinations, clips,
swing arms,
screws, VELCRO, snaps, straps, tape, adhesive, a door, other fasteners, or a
combination
thereof to hold the microfluidic device in or on the platen.
[0004] Fig. 7a is a top view of a rotatable platen 240 having a central axis
of rotation
242 wherein two microfluidic devices 244, 254 can be disposed therein. Each
microfluidic
device can have an input port 246 that can be, for example, teardrop-shaped.
The
enlarged Fig. 7b, taken along line 7b of Fig. 7a, depicts a narrower-end 250
of a teardrop-
shaped chamber 246 radially further from the central axis of rotation 242 of
platen 240,
than a circular first end 248 of teardrop-shaped chamber 246. Microfluidic
device 244 is
disposed in platen 240 such that centerline 252 of platen 240 is parallel to a
length or a
width of rnicrofluidic devices 244, 254. According to various embodiments,
alignment
pinhole 260 and alignment notch 262 can be provided in each microfluidic
device 244,
254. As shown in Fig. 7a, microfluidic device 254 can be to the left of the
centerline 252
of platen 240. Microffuidic device 254 can be left justified in its
orientation. Microfluidic
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device 244 can be to the right of centerline 252. Microfluidic device 244 can
be right-
justified in its orientation. The location of microfluidic devices 244 and 254
with respect
to the centerline 252 of platen 240 can determine a direction in which
teardrop-shaped
chamber 246 is canted. For example, for microfluidic device 244 located to the
right of
the centerline, narrower-end 250 of teardrop-shaped chamber 246 can point
towards the
right, as shown in Fig. 7b. According to various embodiments, the angle of the
cant of the
teardrop-shaped chambers 246 can be the same for all teardrop-shaped chambers
246
formed in a substrate. In another embodiment, narrower-end 250 of teardrop-
shaped
chambers 246 can be radially oriented. Each teaxdrop-shaped chamber 246 can
have a
unique cant. angle.
[00049] _ According to various embodiments, teardrop-shaped chambers 240 can
be
located along a short side of the substrate. The teardrop-shaped chambers 240
can also be
orientated on a long side of the substrate. According to various embodiments,
the
teardrop-shaped chambers 240 can be located at any position within the
substrate such
that the narrower end of the teardrop-shaped chamber is pointed away from the
center of
a platen to direct fluid toward the narrower portion of the teardrop-shaped
chamber 240
and into an adjacent channel, chamber, or well.
[00050] Fig. 8 is a top view of an exemplary microfluidic device 800 having
two input
ports 801, 802 for distributing a fluid sample to respective flow distributors
804, 806, each
flow distributor being in fluid communication with, or being designed to be
valued in
communication with a plurality of pathways. The various wells, chambers,
channels, vial (not
shown), valves, and other features can be manufactured using stereo-
lithography, for example.
The substrate can be cyclic olefin copolymer, or polycarbonate, for example.
Fig. 8 shows an
exemplary microfiuidic device that includes 384 output ports 808. An exemplary
microfiuidic
device can have a feed channel in fluid communication with 96 parallel branch
channels that
form 96 pathways. The pathways can each have a PCR chamber 814, a PCR
purification
chamber 816, a flow restrictor, a vertical flow-sputter that leads to both, a
forward sequencing
chamber 818 and a reverse sequencing chamber 820, a forward sequencing product
purification chamber 822, a reverse sequencing product purification chamber
824, a purified
forward sequencing product 826 output chamber, a purified reverse sequencing
product
output chamber 828, a plurality of opening and closing valves, or a
combination thereof.
Channels, wells, and chambers can be formed in a first and/or a second surface
of the
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microfiuidic device substrate 812. Vias and columns can be used to facilitate
fluid
communication between features formed respectively in the two surfaces of the
device.
[00051] Exemplary spacing for various features in a microffuidic device can be
as described
herein, although other suitable spacing as known to those of ordinary skill in
the art, can also
be used. An exemplary microfiuidic device can have a width of from about 80 to
about 90 mm
The microffuidic device can have a length of from about 115 mm to about 130
mm. Two or
more output wells in the microfiuidic device can be disposed in the substrate
such that a center
of a first output well is about 2.25 mm from a center of a second output well
along a first axis.
Two or more output wells in the microffuidic device can be disposed in the
substrate such that
a center of the first output well is about 0.6 mm, for example, about 0.5625
mm, from a center
of the second output well along a second axis. The substrate for the
microffuidic device can
have a thickness of about 2 mm. One or more output wells and/or processing
chambers in the
microffuidic device can have a depth of about 1.5 mm. One or more output wells
in the
microfiuidic device can have a diameter of about 1.5 mm. One or more
processing chambers in
the microfluidic device can have a depth of about 0.9 rnm. One or more
processing chamber in
the microfluidic device can have a width of about 0.6 mm. One or more
processing chamber in
the microfiuidic device can have a length of about 0.5 mm, about 1.0 mm, about
2.5 mm, or
about 3.5 mm Channels connecting two or more processing chambers and/or an
output wells
can be rectangular-shaped. The channels can have depths of about 0.25 mm. The
channels can
have widths of about 0.25 mm. The channels can have lengths of from about 4 mm
to about
25 mm. The channels can be disposed in the substrate about 0.6 mm, for
example, about
0.5625 mm, from a center of a second channel. The channels can be straight.
The channels can
have one or more turns of any suitable angle or curvature, for example, of
about 150 degrees.
[00052] Further microfiuidic devices, substrates, covers, microfiuidic
manufacturing
methods, input ports, output chambers, pathways, valves, reagents, flow
restrictors, and
methods of use are described in U.S. Patent Application No. to DESMOND et
al., filed January 3, 2003, entitled "Microfiuidic Size-Exclusion Devices,
Systems, and
Methods", Attorney Docket No. 5010-037-O1, and in U. S. Patent Application No.
to BRYNING et al., filed January 3, 2003, entitled "Microfluidic Devices,
Methods, and
Systems", Attorney Docket No. 5010-019-Ol, which are both incorporated herein
in their
entireties by reference.
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[00053] Various advantages and features of a microf(uidic device, system, and
method
have been described herein. Microfluidic devices and systems as described
herein facilitate
the flow of fluids through the microfluidic device when subjected to a
centripetal force.
Flow sputters and flow distributors capable of dividing fluid samples or
reagents into
aliquots are described. The features and methods described herein can be used
with any
microfluidic .device that utilizes centrifugation for fluid transport.
[00054] Those skilled in the art can appreciate from the foregoing description
that the
present teachings can be implemented in a variety of forms. Therefore, while
the teachings
have been described in connection with particular embodiments and examples
thereof, the true
scope of the teachings should not be so limited and various changes and
modifications may be
made without departing from the scope of the teachings.
