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Patent 2493670 Summary

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(12) Patent Application: (11) CA 2493670
(54) English Title: CLOSING BLADE FOR DEFORMABLE VALVE IN A MICROFLUIDIC DEVICE, AND METHOD
(54) French Title: LAME DE FERMETURE DE LA SOUPAPE DEFORMABLE D'UN DISPOSITIF DE MICROFLUIDIQUE, ET PROCEDE ASSOCIE
Status: Dead
Bibliographic Data
(51) International Patent Classification (IPC):
  • B01L 3/00 (2006.01)
  • B01L 99/00 (2010.01)
  • B01L 3/02 (2006.01)
(72) Inventors :
  • COX, DAVID M. (United States of America)
  • BRYNING, ZBIGNIEW T. (United States of America)
(73) Owners :
  • APPLERA CORPORATION (United States of America)
(71) Applicants :
  • APPLERA CORPORATION (United States of America)
(74) Agent: SIM & MCBURNEY
(74) Associate agent:
(45) Issued:
(86) PCT Filing Date: 2003-07-18
(87) Open to Public Inspection: 2004-02-05
Examination requested: 2005-01-21
Availability of licence: N/A
(25) Language of filing: English

Patent Cooperation Treaty (PCT): Yes
(86) PCT Filing Number: PCT/US2003/022553
(87) International Publication Number: WO2004/011132
(85) National Entry: 2005-01-21

(30) Application Priority Data:
Application No. Country/Territory Date
60/398,851 United States of America 2002-07-26
60/398,777 United States of America 2002-07-26
60/398,946 United States of America 2002-07-26
10/336,274 United States of America 2003-01-03
10/336,706 United States of America 2003-01-03
10/403,640 United States of America 2003-03-31
10/403,652 United States of America 2003-03-31
10/426,587 United States of America 2003-04-30

Abstracts

English Abstract




A microfluidic manipulation system is provided that includes a blade for
manipulating deformable material and at least one movable support that is
capable of moving the blade into contact with a microfluidic device including
a deformable feature. When the microfluidic device is operatively held by a
holder, a movable support can position the distal end of the blade relative to
the microfluidic device and move the contact tip surface of the blade such
that it deforms the deformable feature.


French Abstract

L'invention porte sur un système de manipulation de microfluides comportant: une lame pouvant déformer des matériaux déformables, et au moins un support mobile pouvant mettre la lame en contact avec un dispositif microfluidique comprenant un élément déformable. Lorsque le dispositif microfluidique est maintenu par un porteur, le support mobile peut déplacer: l'extrémité distale de la lame par rapport au dispositif microfluidique, ainsi que la surface de contact du bout de la lame pour qu'elle déforme l'élément déformable.

Claims

Note: Claims are shown in the official language in which they were submitted.



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WHAT IS CLAIMED IS:

1. A blade for manipulating deformable material in a microfluidic device, the
blade comprising:
a support end and an opposing distal end, the distal end including an end
blade portion including a first side and a second side angled with respect to
each other at
an angle of from between about 75° and about 110°, wherein each
of the first side and the
second side mutually converge and intersect a contact tip surface at
respective rounded
transition regions, the contact tip surface including a length and a width,
the first side and the
second side being separated from one another at the distal end of the blade by
the length of the
contact tip surface, and wherein the rounded transition regions each include a
radius of
curvature that is from about 70% to about 95% the length of the contact tip
surface;
a third side and a fourth side angled with respect to each other at an angle
of
from about 45° to about 75°, wherein each of the third side and
the fourth side intersect the
contact tip surface and being separated from one another at the distal end of
the blade by the
width of the contact tip surface.

2. The blade of claim 1, wherein the first side and the second side are angled
with
respect to one another at an angle of from about 85° to about
95°.

3. The blade of claim 2, wherein the first side and the second side are angled
with
respect to one another at an angle of from about 87° to about
93°.

4. The blade of claim 1, wherein the rounded transition regions each include a
radius of curvature that is from about 75% to about 90% the length of the
contact tip surface.

5. The blade of claim 4, wherein the rounded transition regions each include a
radius of curvature that is from about 80% to about 85% the length of the
contact tip surface.

6. The blade of claim 1, wherein the third side and the fourth side are angled
with
respect to one another at an angle of from about 50° to about
70°.

7. The blade of claim 6, wherein the third side and the fourth side are angled
with
respect to one another at an angle of from about 55° to about
65°.

8. A microfluidic manipulation system, comprising:
at least one movable support capable of being moved in at least a first
direction
and a second direction;




-18-

at least one blade, the at least one blade including a blade including a body
defined
by a support end and an opposing distal end, the support end being operatively
connected
to the at least one movable support;
a microfluidic device including at least one feature formed therein, the at
least one
feature being defined at least in part by a deformable material;
a holder for holding the microfluidic device;
wherein the distal end of the blade includes an end blade portion including at
least
a first side and a second side that converge to and terminate at a contact tip
surface;
wherein the at least one movable support is adapted to position the distal end
of
the at least one blade relative to the microfluidic device when the
microfluidic device is
operatively held by the holder and is capable of moving the contact tip
surface such that
the contact tip surface contacts the microfluidic device to deform the
deformable material
and to at least partially close the at least one feature.

9. The microfluidic manipulation system of claim 8, wherein the at least one
feature is at least one channel including at least one deformable sidewall.

10. The microfluidic manipulation system of claim 8, wherein the end blade
portion further comprises a third side and a fourth side that converge to and
terminate at
the contact tip surface.

11. The microfluidic manipulation system of claim 10, wherein the contact tip
surface includes a width that extends between the third side and the fourth
side.

12. The microfluidic manipulation system of claim 8, wherein the contact tip
surface includes a curved surface that is defined by a radius.

13. The microfluidic manipulation system of claim 12, wherein the contact tip
surface includes an apex and possesses a linear contact surface at the apex.

14. The microfluidic manipulation system of claim 8, wherein the first side
intersects the contact tip surface at a respective first rounded transition
region and the
second side intersects the contact tip surface at a respective second rounded
transition
region.

15. The microfluidic manipulation system of claim 14, wherein the contact tip
surface includes a length that extends between the first and second rounded
transition
regions.




-19-

16. The microfluidic manipulation system of claim 8, wherein the at least one
blade comprises a plurality of blades, each of the plurality of blades
comprising a
respective body defined by a respective support end and a respective opposing
distal end,
the respective support end of each of the plurality of blades being
operatively connected
to the at least one movable support, and each respective distal end of the
plurality of
blades includes an end blade portion including at least a first side and a
second side that
mutually converge to and terminate at a contact tip surface; and
the at least one movable support is adapted to position at least one of the
plurality
of blades relative to the microfluidic device when the microfluidic device is
operatively
held by the holder, and the at least one movable support is capable of moving
the contact
tip surface of at least one of the plurality of blades such that at least one
respective
contact tip surface contacts the microfluidic device to deform the deformable
material and
at least partially close the at least one feature.

17. The microfluidic manipulation system of claim 16, wherein the at least one
movable support is capable of simultaneously moving the respective contact tip
surfaces
of the plurality of blades into contact with the at least one feature to
simultaneously
deform the deformable material and at least partially close the at least one
feature.

18. The microfluidic manipulation system of claim 16, wherein the at least one
movable support is capable of sequentially moving the respective contact tip
surfaces of
the plurality of blades into contact with the at least one feature to
sequentially deform the
deformable material and at least partially close the at least one feature.

19. The microfluidic manipulation system of claim 16, wherein the end blade
portion of each of the plurality of blades further comprises a third side and
a fourth side
that mutually converge to and terminate at the contact tip surface.

20. A method of closing a feature formed in a microfluidic device, comprising:
providing the microfluidic manipulation system of claim 8, and
moving the support to force the distal end of the blade into contact with the
microfluidic device to deform the deformable material forming the at least one
feature and
at least partially close the at least one feature.

21. A method of at least partially closing at least one feature formed in a
microfluidic device, comprising:
providing the microfluidic manipulation system of claim 16;



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forcing the distal end of at least one of the plurality of blades into contact
with the
microfluidic device to deform the deformable material and at least partially
close the at
least one feature; and
forcing the distal end of at least another one of the plurality of blades into
contact
with the microfluidic device to deform the deformable material and at least
partially close
the at least one feature.

22. The method of claim 21, wherein the plurality of blades are simultaneously
forced into contact with the microfluidic device to simultaneously deform the
deformable
material and at least partially close the at least one feature.

23. The method of claim 21, wherein the plurality of blades are sequentially
forced into contact with the microfluidic device to sequentially deform the
deformable
material and close the at least one feature.

24. The microfluidic manipulation system of claim 8, wherein the contact tip
surface includes a rim and recess.

25. The microfluidic manipulation system of claim 24, wherein the recess
includes a cross-sectional shape that comprises at least one of a~-shape, a U-
shape, a
V-shape, and an at least partially oval shape at an inner periphery of the rim
where the rim
intersects the recess.

26. The microfluidic manipulation system of claim 25, wherein the at least one
movable support is adapted to position the distal end of the blade relative to
the
microfluidic device when the microfluidic device is operatively held by the
holder, and is
capable of moving the contact tip surface such that the contact tip surface
contacts the
microfluidic card to deform the deformable material and at least partially
close the at least
one feature.

27. The microfluidic manipulation system of claim 24, wherein the rim includes
at least two spaced-apart contact tip surface portions, and the at least one
movable
support is capable of moving the at least two spaced-apart contact tip surface
portions
into contact with respective areas of the microfluidic device on opposite
sides of the at
least one feature.

28. The microfluidic manipulation system of claim 27, wherein the rim further
includes an interconnecting rim portion connecting the at least two spaced-
apart contact
tip surface portions.



-21-

29. The microfluidic manipulation system of claim 26, wherein one of the first
side and the second side includes a curved surface.

30. The microfluidic manipulation system of claim 26, wherein one of the first
side and the second side includes a substantially flat surface, the
substantially flat surface
cutting through a portion of the recess formed in the contact tip, surface.

31. A method of closing at least one channel formed in a microfluidic device,
the method comprising:
providing the microfluidic manipulation system of claim 27, and
moving the at least one movable support to force the distal end of the blade
into
contact with the microfluidic device such that the at least two spaced-apart
contact tip
surface portions deform the deformable material and at least partially close
the at least one
channel.

32. A method of closing a channel formed in a microfluidic device, comprising:
providing a microfluidic device including at least one channel formed therein,
wherein the at least one channel is at least partially defined by a deformable
material;
providing at least one first blade including a body defined by a support end
and an
opposing distal end, the distal end terminating at a contact tip surface; and
forcing the distal end of the at least one first blade into contact with the
microfluidic device to deform the deformable material and at least partially
close the at
least one channel.

33. The method of claim 32, whereby the contact tip surface of the at least
one
first blade includes at least two spaced-apart contact tip surface portions
that contact the
microfluidic device on opposing sides of the at least one channel when the
distal end of
the at least one first blade is forced into contact with the microfluidic
device.

34. The method of claim 32, wherein the at least one blade comprises a
plurality of blades, each blade of the plurality of blades including a body
defined by a
support end and an opposing distal end, each opposing distal end terminating
at a
respective contact tip surface; and
forcing the distal ends of the plurality of blades into contact with the
microfluidic
device to deform the deformable material and close the at least one channel.

35. The method of claim 34, wherein the microfluidic device includes a first
area arranged on a first side of the at least one channel, and a second area
arranged on an



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opposing second side of the at least one channel, and wherein at least one of
the plurality
of blades contacts one of the first and second areas and another one of the
plurality of
blades contacts the other of the first and second areas.

36. The method of claim 34, wherein the plurality of blades are simultaneously
forced into contact with the microfluidic device to simultaneously deform
portions of the
deformable material and close the at least one channel.

37. The method of claim 34, wherein the plurality of blades are sequentially
forced into contact with the microfluidic device to sequentially deform
respective portions
of the deformable material and close the at least one channel.

38. The method of claim 32, wherein the at least one channel is defined by at
least one respective sidewall, and the at least one first blade is forced into
contact with the
deformable material at a distance of at least about 0.75 mm from the at least
one
respective sidewall.

39. The method of claim 34, wherein the plurality of blades are spaced apart
from one another about 1.0 cm or less.

40. The method of claim 34, wherein the plurality of blades are spaced apart
from one another about 0.5 cm or less.

41. The method of claim 34, wherein the plurality of blades are spaced apart
from one another about 1.0 mm or less.


Description

Note: Descriptions are shown in the official language in which they were submitted.




CA 02493670 2005-O1-21
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_1_
CLOSING BLADE FOR DEFORMABLE VALVE IN A
MICROFLUIDIC DEVICE, AND METHOD
CROSS REFERENCE TO RELATED APPLICATIONS
[001] This application claims priority benefit from: U. S. Patent Application
No.
10/426,587, filed April 3, 2004; U.S. Patent Applications Nos. 10/,403,652 and
10/403,640, both filed March 31, 2003; U. S. Patent Applications Nos.
10/336,274, and
10/336,706, both filed January 3, 2003; and U.S. Provisional Patent
Applications Nos.
60/398,851, 60/398,777, and 60/398,946, all filed on July 26, 2002. All of the
applications cross-referenced herein are incorporated herein in their
entireties by
reference.
FIELD
[002] The present teachings relate to microfiuidic assemblies, systems, and
devices, and methods for using such assemblies, systems, and devices. More
particularly,
the present teachings relate to assemblies, systems, and devices, and methods
that allow
for the manipulation, processing, and otherwise alteration of micro-sized
amounts of fluid
and fluid samples.
BACKGROUND .
[003] Microfluidic devices are useful for manipulating micro-sized fluid
samples. There continues to exist a need for reliable valuing systems in
microfluidic
devices that enable controlled fluid flow through the microfluidic device. In
particular, a
need exists for devices and methods that achieve quick and relatively simple
actuation of
valves, to promote e~cient processing of fluid samples through microfluidic
devices.
SUMMARY
[004] According to various embodiments, a blade is provided for manipulating
deformable material in a microfluidic device. The blade can include a support
end and an
opposing distal end. The distal end can include an end blade portion including
a first side
and a second side that are angled with respect to each other at an angle of
from between
about 75° and about 110°. The first side and the second side can
mutually converge and
intersect a contact tip surface at respective rounded transition regions. The
contact tip surface
can possess a length and a width. The first side and the second side can be
separated from one
another at the distal end of the blade by the length of the contact tip
surface. The rc>unded
transition regions can each include a radius of curvature that is from about
70% to about



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95% the length of the contact tip surface. A third side and a fourth side of
the blade can be
angled with respect to each other at an angle of from about 45° to
about 75°. Each of the third
side and the fourth side can intersect the contact tip surface and can be
separated from one
another at the distal end of the blade by the width of the contact tip
surface.
[005] According to various embodiments, a microfiuidic manipulation system is
provided including at least one movable blade and at least one movable support
that can
be capable of being moved in at least a first direction and a second
direction. The at least
one movable blade can include a body defined by a support end and an opposing
distal
end. The support end can be operatively connected to the at least one movable
support.
The system can include a microfiuidic device including at least one feature
defined by a
deformable material formed therein. A holder can hold the microfluidic device.
The distal
end of the blade can include an end blade portion including at least a first
side and a
second side that can converge to and terminate at a contact tip surface. The
at least one
movable support can be adapted to position the distal end of the at least one
blade relative
to the microfluidic device when the microfiuidic device is operatively held by
the holder.
The at least one movable support can be capable of moving the contact tip
surface such
that the contact tip surface contacts the microfluidic device to deform the
deformable
material and at least partially close the at least one feature.
[006] According to various embodiments, the microfiuidic manipulation system
can
include a plurality of blades and the at least one movable support can be
adapted to
position at least one of the plurality of blades relative to the microfluidic
device when the
microfluidic device is operatively held by the holder. The at least one
movable support
can be capable of moving the contact tip surface of the at least one of the
plurality of
blades such that at least one respective contact tip surface can contact the
microfluidic
device to deform the deformable material and at least partially close the at
least one
feature.
[007] Methods are also provided for closing at least one feature formed in a
microfluidic device. The methods can include moving the support of the
microfiuidic
manipulation system to force the distal end of the blade into contact with the
microfiuidic
device to deform deformable material forming at least one feature and to at
least partially
close the at least one feature.



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[008] According to various embodiments, the methods can include forcing the
distal
end of at least one of a plurality of blades into contact with a microfluidic
device to
deform a deformable material and to at least partially close at least one
feature of the
device. The method can include forcing the distal end of two or more of the
plurality of
blades into contact with the microfiuidic device to deform the deformable
material and at
least partially close the at least one feature.
[009] According to various embodiments, methods can be provided for closing a
channel formed irl a microffuidic device. The method can include providing a
microfluidic
device including at least one channel formed therein that is at least
partially defined by a
deformable material. At least one first blade can be provided including a body
defined by
a support end and an opposing distal end. The distal end can terminate at a
contact tip
surface. The distal end of the at least one first blade can be forced into
contact with the
microfiuidic device to deform the deformable material and at least partially
close the at
least one channel.
[010] These and other embodiments may be more fully understood with reference
to
the accompanying drawing figures and the descriptions thereof. Modifications
that would
be recognized by those skilled in the art are considered a part of the present
teachings.
BRIEF DESCRIPTION OF THE DRAWINGS
[011] Fig. 1 is a perspective view of a system according to various
embodiments that
includes an opening blade shown in the process of deforming a microfluidic
device;
[012] Fig. 2 is an enlarged view of the system shown in Fig. l, and shows two
sample
wells forming part of a sample processing pathway and that are in fluid
communication with
each other through a connecting channel having a V-shaped cross-section;
[013] Fig. 3 is a side view of a system including an opening blade that has
been
retracted after deforming a portion of a microffuidic device;
[014] Fig. 4 is a perspective view of a system according to various
embodiments and
including a closing blade in the process of deforming a microfiuidic device;
[015] Figs. 5 and 6 are sequential side views of a system according to various
embodiments and including two closing blades before deforming (Fig. 5) and
after deforming
(Fig. 6) a microfiuidic device;



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[016] Fig. 7 is a top view of a deformed microffuidic device according to
various
embodiments includuig a previously open deformable valve that has been closed
by two
closing blades that formed adjacent depressions in the microfluidic device;
[017] Fig. 8 is a top view of a closing blade design according to various
embo diments;
[018] Fig. 9 is a side edge view of the closing blade shown in Fig. 8;
[019] Fig. 10 is an enlarged side edge view of the blade tip end portion of
the closing
blade shown in Fig. 9;
[020] Fig. 11 is an end view of the closing blade shown in Fig. 8;
[021] Fig. 12 is an enlarged view of the blade tip end portion of the closing
blade
shown in Fig. 1 l;
[022] Fig. 13 is a top view of a closing blade design according to various
embodiments;
[023] Fig. 14 is a side edge view of the closing blade shown in Fig. 13;
[024] Fig. 15 is an enlarged view of the blade tip end portion of the closing
blade
shown in Fig. 14 and taken along line 34' in Fig. 14;
[025] Fig. 16 is an end view of the closing blade shown in Fig. 13;
[026] Fig. 17 is an enlarged view of the blade tip end portion of closing
blade shown
in Fig. 16;
[027] Fig. 18 is a side view of a system according to various embodiments and
incorporating the closing blade shown in Figs. 13-17 positioned for a
defornvng operation on a
microffuidic device; and
[028] Fig. 19 is a perspective view of a microfluidic manipulation system
according to
various embodiments and including a stack of closing blades arranged on a
moveable support,
and a microffuidic card arranged on a holder.
DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS
[029] Fig. 1 is a perspective view of a microfluidic manipulation system that
can be used
to manipulate micro-sized fluid samples. The system can include a microfluidic
device 10 that
includes a disk or substrate 18 and a pathway formed therein that is at least
partially formed of
a deformable material, for example, an inelastically deformable material. The
substrate 18
of the microfluidic device 10 can include a plurality of sample wells 14
formed therein. The
substrate 18 can be in the shape of a disk, or a rectangular or square card,
or can have any



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other shape. The sample wells are exemplary of features that can be included
in or on the
microfluidic device 10. Other features that can be included in or on the
microfluidic device 10
include reservoirs, recesses, channels, vias, appendices, output wells,
purification columns,
valves, and the like.
[030] As shown in Fig. 1, the plurality of sample wells 14 can be arranged
generally
linearly in a series, with each series forming a sample processing pathway. At
one end of each
sample processing pathway, a sample well or input chamber 13 can be provided
for the
introduction of fluid samples. The input chamber 13 can include a U-shaped-
cross-sectioned
channel or reservoir that includes an input port 15 arranged at one end
thereof. According to
various embodiments, and as shown in Fig. 1, more than one series constituting
a respective
sample processing pathway can be arranged side-by-side in or on the substrate
such that a
plurality of samples can be simultaneously processed on a single microfluidic
device 10. For
example, 96 sample processing pathways can be arranged side-by-side to form a
set of
processing pathways on a microffuidic device 10. Moreover, two or more sets of
96 sample
processing pathways, for example, can be arranged on a single microfluidic
device 10.
[031] As shown in Fig. 1, portions of the substrate 18 can form intermediate
walls 16
that can interrupt fluid communication between adjacent sample wells 14 in a
series or
pathway, when the intermediate walls 16 are in a non-deformed state. The
intermediate walls
16 can be forcibly deformed with an opening blade 12 to selectively achieve
fluid
communication 11 between two or more adjacent sample wells 14 of a sample
processing
pathway. By selectively arranging sample well 14 in respective series, micro-
sued fluid
samples can be sequentially processed through the respective sample processing
pathways
from one sample wells 14 to an adjacent sample well, and so on through the
respective
pathway. According to various embodiments, the opening blades can be made from
a
relatively rigid material. Stainless steel and haxd aluminum can be used, for
example, to
form an opening blade.
[032] Fig. 2 is an enlarged view of the microfluidic device 10 shown in Fig.
1, and
illustrates a portion of a sample processing pathway that includes two sample
wells 14a, 14b
formed in the substrate 18. In a non-deformed state (not shown) of the
substrate 18, fluid
communication between the two sample wells 14a, 14b can be prevented,
interrupted, or
obstructed, by the intermediate wall 16 located between the sample wells 14a,
14b. The
intermediate wall 16 can be at least partially formed from a deformable
material, for



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example, an inelastically deformable material. According to various
embodiments, the
inelastically deformable material forming the intermediate wall 16 can be the
same
material used to form the substrate 18, and can be an integral part of the
substrate 18.
The inelastically deformable material forming the intermediate wall 16 can be
selectively
deformed by an opening blade tip, such that a depression or channel 19 can be
formed
that extends between the two sample wells 14a, 14b, to thereby create a fluid
communication between the two sample wells 14a, 14b.
[033] As shown in Fig. l, the surface of the substrate 18 formed with sample
wells
14 can be covered with an elastically deformable cover sheet 20. The cover
sheet 20 can
be made of, for example, a plastic, elastomeric, or other elastically
deformable material. If
included, the elastically deformable cover sheet 20 can be attached to the
substrate 18
with an adhesive, for example, a layer of a pressure sensitive adhesive, a hot
melt
adhesive, or the like. Alternatively, the elastically deformable cover sheet
20 can be
attached to the substrate 18 with another attachment mechanism, for example, a
heat
weld, clamps, screws, nails, by friction-fit, or the like. According to
various
embodiments, either one of, or both of, the elastically deformable cover sheet
20 and the
adhesive, can be transparent and/or translucent. Alternatively, according to
various
embodiments, either one of or both of the elastically deforrnable cover sheet
20 and the
adhesive can be opaque, non-transparent, and/or non-translucent.
[034] According to various embodiments, the microfluidic device 10 can form a
part of a
microfiuidic assembly or system 38, as shown in Fig. 19 as discussed below.
[035] A system or assembly according to various embodiments can include a
variety
of deforming blades, for example, one or more opening blades and/or one or
more closing
blades. Such systems can be used in connection with microfluidic assemblies
that can
include at least one sample processing pathway, including at least two sample-
containing
features that can be placed in fluid communication with one another.
[036] Referring to Fig. l, when it is desired to transfer a fluid sample from
one sample
well 14 to another sample well 14, a movable support can force at least one
opening blade 12
into contact with the elastically deformable cover 20 of the microfluidic
device 10 in an area
adjacent the intermediate wall 16. A blade tip portion 26 of the opening blade
12 can force the
elastically deformable cover 20 into the deformable material of the
intermediate wall 16. When
forced into the intermediate wall 16 with a sufficient force, the blade tip
portion 26 of the



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_7_
opening blade 12, with the elastically deformable cover 20 in between, can
form a depression
19 in the intermediate wall 16, as shown in Fig. 2.
[037] Fig. 3 is an end view of an opening blade 12 according to various
embodiments and illustrates the opening blade 12 after contacting and forming
a
depression 19 in a microfluidic device 10. Upon fully retracting the opening
blade 12, the
elastically deformable cover 20 rebounds at least partially back toward its
initial
substantially planar orientation, while the deformable material of the
substrate 18, if less
elastic than the cover 20, remains deformed. As a result, a channel 22 is
formed, defined
by the cover 20 and the depression 19, and extending between the sample wells
14. As
shown in Figs 2 and 3, the depression 19 can be defined by a sidewall
including a first
sidewall portion 19a and a second sidewall portion 19b.
[038] Fig. 2 illustrates a close-up, perspective view of the depression 19
formed in
the substrate 18 by an opening blade 12. According to various embodiments, the
depression 19, and, in turn, the sidewalls 19a and 19b thereof, can exhibit a
variety of
cross-sectional shapes depending upon the blade tip design of the opening
blade 12. For
example, an opening blade design including a straight edge, a chisel-edge, or
a pointed-
blade design, can be used to form the depression 19 in the disk portion 18.
According to
various embodiments, the shape of the blade tip portion 26 of the opening
blade 12, and the
force applied to the microfluidic device 10 by the opening blade 12 are
designed to prevent the
opening blade 12 from cutting or ripping through the cover 20.
[039] Accordingly, a deformable portion of a microfluidic device 10 can be
deformed by an opening blade 12 to establish fluid communication between
sample wells
14. The deformable portions can be parts of a deformable valve of the type
described in
U.S. Patent Application No. 10/398,851 filed July 26, 2002, which is
incorporated herein
in its entirety by reference, and which are referred to herein as Zbig valves.
[040] Various structural properties and characteristics of the components of
the
microfluidic assembly, for example, the substrate 18 material, the cover 20
material, and
the adhesive component can be as disclosed in U.S. Provisional Application No.
60/398,851.
[041] The substrate 18 of the microfluidic device 10 can include a single
layer of
material, a coated layer of material, a mufti-layered material, and
combinations thereof.
More particularly, the substrate 18 can be formed as a single-layer and made
of a non-



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_g_
brittle plastic material, such as polycarbonate, or a TOPAZ material, a
plastic cyclic olefin
copolymer material available from Ticona (Celanese AG), Summit, New Jersey,
USA.
[042] The elastically deformable cover 20 can possess elastic properties that
enable it
to be temporarily deformed when contacted by a deforming blade. However, in
contrast
to the more inelastically defonnable material of the substrate 18, the
elastically deformable
cover layer 20 can more or less return to an original orientation to an extent
su~cient to
achieve fluid communication between underlying sample wells 14. PCR tape
materials
can be used as, or with, the elastically deformable cover 20. Polyolefinic
films, other
polymeric films, copolymeric filins, and combinations thereof can be used, for
example, to
form the elastically deformable cover layer 20.
[043] According to various embodiments, the materials forming the components
of
the microfluidic device can be capable of withstanding thermal cycling at
temperatures of
from about 60° C to about 95° C, as, for example, the
microfluidic device 10 would be
exposed to if the device is used to perform polymerase chain reactions (PCR).
Furthermore, the materials forming the components of the microffuidic device
10 can
possess a strength such that the microfluidic device 10 can withstand forces
that are
applied when forcing fluid samples therethrough. For example, the materials
forming the
components of the microfluidic device 10 can withstand centrifugal forces
encountered
when spinning the microffuidic device 10 and sequentially forcing samples from
one
sample well 14 to another by centripetal motion.
[044] According to various embodiments, alter opening a Zbig valve 24 by way
of an
opening blade 12, a fluid sample held in an initial sample well can be forced
to move through
the resultant channel 22 and into an adjacent sample well. 'The fluid sample
can be forced to
move by way of centripetal or gravitational force, for example. The
microfluidic device 10
can be attached to a rotatable platen and spun, whereby centripetal force
causes a fluid
sample to move through the open channel 22 from a radially inwardly arranged
sample
well to a radially outwardly arranged sample well.
[045] According to various embodiments, to continue processing the fluid
sample in
the radially outwardly arranged sample well, for example, to perform a
polymerase chain
reaction (PCR), it can be desirable to close the Zbig valve 24 to prevent
fluid sample from
migrating back into the radically inward sample well. According to various
embodiments
and as shown in Fig. 4, a closing blade 30 can be provided to plastically
deform or cold-



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form the deformable material forming the channel 22 of the open Zbig valve
2.4. In
particular, a closing blade 30 can be used alone, or in combination with one
or more
additional closing blades, to quicldy and simply form a barrier wall or dam of
deformable
material between the sample wells 14. 'The barrier wall can at least partially
prevent fluid
communication between sample wells 14, thereby reducing the possibility of the
fluid
sample undesirably migrating back into the sample well in which the fluid
sample was
previously held in.
[046] According to various embodiments, the deformable material of the
substrate 18
can be struck on either side, both sides, or within or across the width of the
area of the channel
22 portion of the open Zbig valve 24. One or more closing blades 30 can be
used to strike the
microfluidic device 10 in either a sequential or simultaneous manner, or in a
combination
thereof.
[047] For example, Figs. 5 and 6 sequentially illustrate a side view of an
arrangement
including two closing blades 30 deforming a microffuidic device 10. At least
the blade tip
portions 34 of the closing blades 30 can be forced into contact with the
microfluidic card 10 in
or near the open channel 22 of the Zbig valve 24 to at least partially close
the channel 22.
[048] According to various embodiments, the closing blade 30 can contact
deformable
material that was not previously deformed during a channel formation step. For
example, as
shown in Fig. 5, a closing blade 30 can strike the microffuidic device 10 a
set distance, X, from
a sidewall 19a, 19b of a channel 22. The distance, X, can correspond to at
least about
0.75 mm from either sidewall 19a, 19b, for example. According to various
embodiments, the
distance, ~, can vary proportionally as a function of the size of the sample
wells and the size of
the depression 19 formed in the intermediate wall.
[049] As sequentially shown in Figs. 5 and 6, the one or more blade tip
portions 34 of
the.respective one or more closing blades 30 can displace the deformable
material of the
substrate 18 when used to form impressions 36 in the substrate 18. By creating
impressions 36 in relatively close proximity to the sidewalls 19a, 19b of the
depression 19,
material defining the sidewalls of the depression 19 can be deformed, for
example, bulged
inwardly, as shown by the arrows arranged in pairs at 37 and 39. As a result,
a barner
wall 40 can be formed between two sample wells 14. Depending upon, for
example, the
number of blades used and the shape of the blade tip portions 34, the bulging
deformation



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of the sidewalls 19a, 19b can be varied to either fully or partially close
fluid
communication between two adjacent sample wells 14.
[050] According to various embodiments, by forming the impressions 36, and in
turn
forming the barrier wall 40, the deformable material forming the barrier wall
40 can be
forced to achieve a fluid-tight seal between the cover 20 and the barrier wall
40, thus
interrupting fluid communication between the adjacent sample wells 14. The
deformable
material forming the barrier wall 40 can be forced into contact with a
pressure sensitive
adhesive layer that is arranged between the cover 20 and the substrate 18.
[051] Fig. 7 is a top view of a microffuidic device 10 that includes a
previously open
Zbig valve 24 that has been closed by way of deformations caused by two
closing blades
that straddle the valve 24. Two impressions 36, each formed by a respective
closing
blade 30 striking the microfluidic device 10, are illustrated. An impression
36 can be
formed on either side or both sides of the channel of the previously open Zbig
valve 24,
and each impression 36 can be spaced a set distance from a sidewall 19a, 19b
of the
depression 19, as discussed above. The formation of the impressions 36 causes
the
sidewalls 19a, 19b of the Zbig valve channel to be pushed closed thereby
deformably
creating the barrier wall 40 and collapsing the sidewalk into contact with one
another.
The hot dog bun-shaped deformation in Fig. 7 illustrates the Zbig valve
channel in a
closed condition. More particularly, the sidewalls 19a, 19b are shown in
contact with
each other at 39.
[052] With the Zbig valve 24 closed and fluid communication between the sample
wells interrupted, it is possible to continue processing a fluid sample
situated in the
radially outwardly sample well without having the fluid sample migrate back
into a
previously occupied radially inward sample well.
[053] Figs. 8 to 17 illustrate several closing blade designs according to
various
embodiments. A blade tip portion 34 of a closing blade 30 can be provided with
a closing
blade designed to provide desired deformation to a deformable material, such
as the material of
a microfluidic device substrate. For example, the blade tip portion 34 can
possess a shape
that leaves an impression in a deformable material that causes features, such
as the
sidewalls of a channel, to deform and form a barrier wall between two
previously joined
sample wells. According to vaxious embodiments, the closing blades can be made
from a



CA 02493670 2005-O1-21
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relatively rigid material. Stainless steel and hard aluminum can be used, for
example, to
form a closing blade.
[054] Fig. 8 is a side view of a closing blade according to various
embodiments. The
closizig blade 30 can include at least four side surfaces; a first side
surface 60, a second
side surface 70, a third side surface 80, and a fourth side surface 90 (not
shown in Fig. 8).
Each side includes a length extending from a support end 50 of the closing
blade 30 to a
distal end 58 of the closing blade 30.
[055] The support end 50 of the closing blade 30 can include a main body
portion
52. The main body portion 52 can include a connection mechanism for connecting
the
closing blade 30 to a moveable support. The moveable support can be, for
example, an
actuator for moving the closing blade 30 into and out of deformable contact
with a
microffuidic device 10. Such a moveable support 32 is shown in Fig. 19. The
connection
mechanism of the closing blade 30 can be a feature that allows the closing
blade 30 to be
securely fastened to the moveable support, such as one or more apertures 56
for threading
or passing connecting bolts therethrough.
[056] As shown in Figs. 8 and 9, each of the first side surface 60, second
side
surface 70, third side surface 80, and fourth side surface 90, includes a
first portion and a
respective second angled portion that is angled relative to the first portion.
For example;
first side surface 60 includes first portion 62 and respective angled portion
64; second side
surface 70 includes first portion 72 and respective angled portion 74; third
side surface 80
includes first portion 82 and respective angled portion 84; and fourth side
surface 90
includes first portion 92 and respective angled portion 94.
[057] According to various embodiments, first side surface 60 and second side
surface 70 can oppose one another and can include respective first portions
62, 72, that
possess lengths that are longer, shorter, or the same, as the lengths of
respective first
portions 82, 92 of the third side surface 80 and the fourth side surface 90.
Moreover,
third side surface 80 and fourth side surface 90 can oppose one another, or
alternatively,
respective first portions 82, 92 of the third side surface 80 and fourth side
surface 90;
respectively, can oppose each other.
[058] The first portions 62, 72 of the respective first and second side
surfaces 60, 70
can extend parallel to one another, as illustrated in Fig. 8. The first
portion 62 of the first
side surface 60 can include a length that differs from the length of the first
portion 72 of



CA 02493670 2005-O1-21
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_12_
the second side surface 70. Correspondingly, the first portions 82, 92 of the
respective
third and fourth side surfaces 80, 90 can be parallel to one another, as
illustrated in Fig. 9
that shows a side view of the closing blade of Fig. 8. The first portion 82 of
the third side
surface 80 can have a length that differs from the length of the first portion
92 of the
fourth side surface 92.
[059] As shown in Fig. 8, the distal end 58 of the closing blade 30 can
include a
blade tip portion 34. Along the blade tip portion 34, a first side angled
portion 64 and a
second side angled portion 74 are angled with respect to one another such that
they
mutually converge and intersect at a contact tip surface 100, at respective
rounded transition
regions 102, 104. Accordingly, each of the first side surface 60 and the
second side
surface 70 can terminate at the distal end 58 of the closing blade 30 at a
respective
rounded transition region 102, 104. The first side angled portion 64 and the
second side
angled portion 74 can be angled with respect to each other at an angle of from
about 75°
to about 110°, or from about 85° to about 95°, or from
about 87° to about 93°.
[060] Fig. 9 is a side view of the closing blade 30 shown along a length of
the blade.
As shown, first portion 82 of third side surface 80 and first portion 92 of
the fourth side
surface 90 are shown opposing one another. Moreover, at the distal end 58 of
the closing
blade 30, third side angled portion 84 and fourth side angled portion 94 can
be angled
with respect to one another such that they mutually converge and intersect at
a contact tip
surface 100. The third side angled portion 84 and the fourth side angled
portion 94 can
be angled with respect to each other at an angle of from about 45° to
about 75°, or from
about 50° to about 70°, or from about 55° to about
65°.
[061] Fig. 10 is an enlarged view of the blade tip portion 34 of the closing
blade 30
shown in Fig. 9. The contact tip surface 100, formed at the converging ends of
third side
angled portion 84 and fourth side angled portion 94, can include a curved
surface that can
be defined by a radius of curvature, R. The radius of curvature, R, of the
contact tip
surface 100 can be a value of from about 0.0025 inch to about 0.0125 inch, a
value of
from about 0.0050 inch to about 0.0100 inch, or a value of about 0.0075 inch.
The
contact tip surface 100 can include an apex 101 at the distal tip thereof, and
the apex 101
can provide a linear contact surface along a length of the contact tip surface
100.
[062] Fig. 11 is an end view of the distal end 58 of the closing blade 30 of
Fig. 8.
The contact tip surface 100 is shown as being formed at and defined by the
ends of the



CA 02493670 2005-O1-21
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-13-
two pairs of mutually converging side angled portions. Specifically, the
contact tip
surface 100 can be formed at the end of the mutually converging first side
angled portion
64 and second side angled portion 74, and at the end of the mutually
converging third side
angled portion 84 and fourth side angled portion 94.
[063] Fig. 12 is an enlarged view of the blade tip portion 34 of the closing
blade 30
shown in Fig. 11. As shown in Fig. 12, the contact tip surface 100 can possess
a length,
L, and a width, W. The length, L, can extend between an end of the first side
angled
portion 64, and an end of third side angled portion 74. Moreover, the width,
W, can
extend between an end of third side angled portion 84, and an end of fourth
side angled
portion 94. Ridges 132, 134, 136, and 138 can be formed at respective
intersections of
adjacent angled portions, for example, at the intersection of first side
angled portion 64 and
fourth side angled portion 94, or at the intersection of fourth side angled
portion 94 and the
second side angled portion 74.
[064] Fig. 12 illustrates the first side angled portion 64 and second side
angled
portion 74 intersecting the contact tip surface 100 at respective rounded
transition regions
102, 104. According to various embodiments, the rounded transition regions
102, 104 can
each possess a radius of curvature that is from about 70% to about 95%, or
from about 75%
to about 90%, or from about 80% to about 85%, the length, L, of the contact
tip surface 100.
The radius of curvature of each of the rounded transition regions 102, 104 can
be a value
of from about 0.025 inch to about 0.075 inch, a value from about 0.035 inch to
about
0.065 inch, or a value of about 0.050 inch.
(065] Figs. 13-17 illustrate various views of a closing blade 30' with a
modified
closing blade design according to various embodiments. Features of the closing
blade 30'
that are similar to those of closing blade 30, bear the same numeral but are
succeeded by a
prime "' " symbol. For example, as shown iti Figs. 13 and 14 and similar to
closing
blade 30, closing blade 30' can include at least four side surfaces; a first
side surface 60', a
second side surface 70', a third side surface 80', and a fourth side surface
90'. Each side
can possess a length that extends from a support end 50' of the closing blade
30' to a
distal end 58' of the closing blade 30'. Similar to closing blade 30, the
support end 50' of
the closing blade 30' can include a main body portion 52' including a
connection
mechanism for connecting the closing blade 30' to a moveable support, such as
moveable
support 32 as shown.



CA 02493670 2005-O1-21
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-14-
[066] As shown in Fig. 13, each of the first side surface 60' and the second
side
surface 70', can include a respective first angled portion and a respective
second angled
portion that can be angled relative to the first portion. For example, first
side surface 60'
can include first portion 62' and a respective angled portion 64', and second
side surface
70' can include first portion 72' and a respective angled portion 74'. Fig. 14
shows that
third side surface 80' and fourth side surface 90' can each extend to a
contact tip surface
100' located at the distal end 58' of the closing blade 30'. According to
various
embodiments, each of the sides of closing blade 30' can exhibit the
characteristics, such as
lengths, widths, angles, for example, as disclosed for the comparable
characteristics of
closing blade 30, as previously disclosed above.
[067] As shown in Fig. 13, first side angled portion 64' and second side
angled
portion 74' can be angled with respect to one another such that they mutually
converge and
intersect the contact tip surface 100'. The first side angled portion 64' and
the second side
angled portion 74' can be angled with respect to each other at an angle of
from about 75°
to about 110°, or from about 85° to about 95°, or from
about 87° to about 93°.
[068] Fig. 14 is a side view of the closing blade 30' along a length of the
blade. As
shown, third side surface 80' and fourth side surface 90' are shown in an
opposing
relationship to one another, and can be arranged to be parallel to one
another. At the
distal end 58' of closing blade 30', the third side surface 80' and the fourth
side surface 90'
terminate at the contact tip surface 100'. As shown in Figs 13 and 14, second
side angled
portion 74' can be cut along a plane 120 such that the plane 120 can cut
through a portion
of the recess 110 formed in the contact tip surface 100'. Alternatively,
second side angled
portion 74' can be arranged to be a substantially straight, fiat sided surface
that is angled
to cut through a portion of the recess 110 of the contact tip surface 100'. As
a result, the
recess 110 can be at least partially open at a side of the contact tip surface
100', as shown
in Figs. 14 and 15.
[069] Fig. 15 is an enlarged side view of the blade tip portion 34' of closing
blade 30'
shown in Fig. 14. Contact tip surface 100' can include a rim 112 including an
inner
periphery partially defined by a recess 110. The rim 112 can include a
substantially flat
surface and can be at least partially defined by two spaced-apart contact tip
surface
portions 114, 116.



CA 02493670 2005-O1-21
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-15-
[070] Fig. 16 is an end view of the distal end 58' of closing blade 30' of
Fig. 13. As
shown, first side angled portion 64' and second side angled portion 74' can
mutually
converge to partially define a portion of the contact tip surface 100'.
[071] Fig. 17 is an enlarged view of the blade tip portion 34' of closing
blade 30'
shown in Fig. 16. The perimeter of the rim 112 of the contact tip surface 100'
can be
defined at least by an end of the first side angled portion 64', an end of the
second side
angled portion 74', an end of the third side surface 80', an end of the fourth
side surface
90', and by the recess 110. Along an inner periphery 113 of the rim 112, where
the rim
112 intersects the recess 110, the recess 110 can possess a cross-sectional
shape that
includes at least one of a U-shape, a U-shape, a V-shape, and an at least
partially oval
shape. At a closed end of the recess 110, the recess 110 can include a radius
of curvature,
R', of from about 0.010 inch to about 0.050 inch, or from about 0.015 inch to
about 0.030
inch. Moreover, the rim 112 can include at least two spaced-apart contact tip
surface
portions 114, 116 that can be connected by an interconnecting rim portion 118
to form
the substantially planar contact tip surface 100'.
[072] According to various embodiments, the first side angled portion 64' can
possess a curved surface along a length thereof. The curved surface can define
a curved
outer perimeter 122 of the interconnecting rim portion 118 at an intersection
of an end of
the first side angled portion 64' and the rim 112 of the contact tip surface
100'. By
incorporating a curved outer perimeter 122 along the interconnecting rim
portion 118,
closing blade 30' can be forced into the microfluidic card 10 without cutting
or ripping
through the cover 20' along the interconnecting rim portion 118.
[073] Fig. 18 shows a side view of an arrangement including a closing blade
30' that can
be forced into contact with a microfluidic device 10' to deformably close an
open channel 22.
The closing blade 30' can be arranged such that when its contact tip surface
100' is forced into
defornlable contact the microffuidic device 10', each of the at least two
spaced-apart contact
tip surface portions 114, 116 of the rim 112 contact deformable material that
has not
previously been deformed during the formation of the channel 22. For example,
the spaced-
apart contact tip surface portions 114, 116 can strike the microfiuidic device
10 a set
distance, X, such as at least about 0.75 mm from a sidewall 19a, 19b of the
channel 22.
According to various embodiments, the distance, X, can vary proportionally as
a fimction of
the size of the sample wells and the size of the depression 19 formed in the
intermediate wall.



CA 02493670 2005-O1-21
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-16-
Moreover, the interconnecting rim portion 118 of the contact tip surface 100'
can be forced
into the microfluidic card 10 in an area that traverses across the width of
the depression 19.
[074] The contact tip surface 100' including the spaced-apart contact tip
surface
portions 114, 116 and the intercomiecting rim portion 118, along with a
portion of the
surface of the recess 110, can cause the material defining the sidewalls 19a,
19b to be
deformed. For example, the material defining the sidewalls 19a, 19b can be
forced to
bulge inwardly, to form a barrier wall between two sample wells 14. Moreover,
the
interconnecting rim portion 118 can simultaneously deform one or more
respective portions of
the sidewalk 19a, 19b to form part of the barrier wall.
[075] As in the previously described embodiments, the barrier wall formed by
closing
blade 30' can to achieve a fluid-tight seal between the cover 20 and the
barrier wall,
thereby interrupting fluid communication between the sample wells 14.
According to
various embodiments, deformable material forming the barrier wall can be
forced into
contact with the partially deformed pressure sensitive adhesive layer to
achieve the fluid-
type seal.
[076] As shown in Fig. 19, the microfiuidic device 10 can be capable of being
contacted
and deformed by a deforn~ing blade or a plurality of stacked deforming blades
30 attached to a
movable support 32. According to various embodiments, a supporting device,
such as, for
example, a holder plate 34 can be used to securely support the microfluidic
device 10 in
relation to both the movable support 32 and the deformiing blades 30 of the
microffuidic
assembly or system 38.
[077] Various components, systems, and methods that can be used in conjunction
with the closing blades, systems, and methods described herein, include the
features and
methods described in U.S. Provisional Patent Applications Nos. 60/398,777,
60/398,851,
60/399,548, and 60/398,946, and in U.S. Patent Applications Nos. 10/336,274,
10/336,706, and 10/336,330, all of which are herein incorporated in their
entireties by
reference.
[078] 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
these teachings
have been described in connection with particular embodiments and examples
thereof, the true
scope of the present teachings should not be so limited. Various changes and
modifications
may be made without departing from the scope of the teachings herein.

Representative Drawing
A single figure which represents the drawing illustrating the invention.
Administrative Status

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Administrative Status

Title Date
Forecasted Issue Date Unavailable
(86) PCT Filing Date 2003-07-18
(87) PCT Publication Date 2004-02-05
(85) National Entry 2005-01-21
Examination Requested 2005-01-21
Dead Application 2007-07-18

Abandonment History

Abandonment Date Reason Reinstatement Date
2006-07-18 FAILURE TO PAY APPLICATION MAINTENANCE FEE

Payment History

Fee Type Anniversary Year Due Date Amount Paid Paid Date
Request for Examination $800.00 2005-01-21
Registration of a document - section 124 $100.00 2005-01-21
Application Fee $400.00 2005-01-21
Maintenance Fee - Application - New Act 2 2005-07-18 $100.00 2005-01-21
Owners on Record

Note: Records showing the ownership history in alphabetical order.

Current Owners on Record
APPLERA CORPORATION
Past Owners on Record
BRYNING, ZBIGNIEW T.
COX, DAVID M.
Past Owners that do not appear in the "Owners on Record" listing will appear in other documentation within the application.
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Document
Description 
Date
(yyyy-mm-dd) 
Number of pages   Size of Image (KB) 
Abstract 2005-01-21 2 67
Claims 2005-01-21 6 307
Drawings 2005-01-21 8 274
Description 2005-01-21 16 973
Representative Drawing 2005-01-21 1 10
Cover Page 2005-03-24 1 43
PCT 2005-01-21 2 118
Assignment 2005-01-21 6 323