U.S. patent application number 11/251351 was filed with the patent office on 2006-02-16 for reaction chamber roll pump.
Invention is credited to John F. McEntee.
Application Number | 20060035271 11/251351 |
Document ID | / |
Family ID | 25103045 |
Filed Date | 2006-02-16 |
United States Patent
Application |
20060035271 |
Kind Code |
A1 |
McEntee; John F. |
February 16, 2006 |
Reaction chamber roll pump
Abstract
A method and system for circulating sample solution within a
reaction chamber containing a microarray. The reaction chamber
contains, on each side, a shallow vertical and a deep vertical well
at the corners of the microarray. The vertical wells having a gap
between the active surface of the microarray and the bottom of the
reaction chamber are filled with sample solution. As the reaction
chamber is rotated, sample solution from the deep vertical well
displaces sample solution in the gap between the active surface of
the microarray and the bottom of the reaction vessel, and sample
solution from that gap is, in turn, displaced into the shallow
vertical well, from which it flows along the inner surface of a
cover strip above the microarray back to the deep vertical
well.
Inventors: |
McEntee; John F.; (Boulder
Creek, CA) |
Correspondence
Address: |
AGILENT TECHNOLOGIES, INC.;INTELLECTUAL PROPERTY ADMINISTRATION, LEGAL
DEPT.
P.O. BOX 7599
M/S DL429
LOVELAND
CO
80537-0599
US
|
Family ID: |
25103045 |
Appl. No.: |
11/251351 |
Filed: |
October 13, 2005 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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10837334 |
Apr 30, 2004 |
|
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|
11251351 |
Oct 13, 2005 |
|
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09775012 |
Jan 31, 2001 |
6746649 |
|
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10837334 |
Apr 30, 2004 |
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Current U.S.
Class: |
435/6.11 ;
435/287.2 |
Current CPC
Class: |
B01L 3/502 20130101;
B01J 2219/00659 20130101; B01F 2215/0037 20130101; B01F 13/0059
20130101; C40B 60/14 20130101; B01L 2400/0457 20130101; Y10T 436/25
20150115; F04B 19/006 20130101; B01J 2219/00484 20130101; B01J
2219/00596 20130101; B01L 2300/0822 20130101; C40B 40/06 20130101;
B01J 2219/00722 20130101; B01J 2219/00585 20130101; B01L 2300/0636
20130101; B01J 2219/00576 20130101; B01J 2219/00527 20130101; B01J
2219/00605 20130101; B01F 9/0021 20130101; Y10T 436/2575 20150115;
B01J 2219/00488 20130101 |
Class at
Publication: |
435/006 ;
435/287.2 |
International
Class: |
C12Q 1/68 20060101
C12Q001/68 |
Claims
1-28. (canceled)
29. A method of moving a fluid within a reaction chamber, said
method comprising: introducing a fluid into said reaction chamber,
wherein said reaction chamber comprises a roll pump; and rotating
said reaction chamber about a rotation axis so that said roll pump
provides for continuous fluid flow in said reaction chamber.
30. The method according to claim 29, wherein said roll pump
comprises: a shallow vertical well connected to a deep vertical
well by an inclined feature.
31. The method according to claim 30, wherein said reaction chamber
further comprises a reactive entity.
32. The method according to claim 31, wherein said rotation axis is
perpendicular to an edge of said reactive entity.
33. The method according to claim 32, wherein said reactive entity
is a microarray of molecular species.
34. The method according to claim 33, wherein said molecular
species are nucleic acids.
35. The method according to claim 29, wherein said rotating is
continuous.
36. The method according to claim 29, wherein said fluid is a
sample.
37. The method according to claim 29, wherein said fluid is a wash
fluid.
38. The method according to claim 29, wherein said fluid comprises
labeled molecules.
39. The method according to claim 38, wherein said labeled
molecules are fluorescently labeled.
40. A method of moving a fluid within a reaction chamber comprising
a nucleic acid microarray, said method comprising: introducing a
fluid into said reaction chamber, wherein said reaction chamber
comprises a roll pump; and rotating said reaction chamber about a
rotation axis so that said roll pump continuously moves fluid over
an active surface of said nucleic acid array.
41. The method according to claim 40, wherein said roll pump
comprises: a shallow vertical well connected to a deep vertical
well by an inclined feature.
42. The method according to claim 40, wherein said rotation axis is
perpendicular to an edge of said nucleic acid microarray.
43. The method according to claim 40, wherein said rotating is
continuous.
44. The method according to claim 40, wherein said fluid is a
sample.
45. The method according to claim 40, wherein said fluid is a wash
fluid.
46. The method according to claim 40, wherein said fluid comprises
labeled molecules.
47. The method according to claim 46, wherein said labeled
molecules are fluorescently labeled.
Description
TECHNICAL FIELD
[0001] The present invention relates to small reaction chambers,
such as a reaction chamber including a microarray within a
microarray strip, and, in particular, to a method and system for
circulating solutions within small sealed reaction chambers.
BACKGROUND OF THE INVENTION
[0002] Microarrays are widely used and increasingly important tools
for rapid hybridization analysis of sample solutions against
hundreds or thousands of precisely ordered and positioned features
on the active surfaces of microarrays that contain different types
of molecules. Microarrays are normally prepared by synthesizing or
attaching a large number of molecular species to a chemically
prepared substrate such as silicone, glass, or plastic. Each
feature, or element, on the active surface of the microarray is
defined to be a small, regularly-shaped region on the surface of
the substrate. The features are arranged in a regular pattern. Each
feature may contain a different molecular species, and the
molecular species within a given feature may differ from the
molecular species within the remaining features of the microarray.
In one type of hybridization experiment, a sample solution
containing radioactively, fluorescently, or chemoluminescently
labeled molecules is applied to the active surface of the
microarray. Certain of the labeled molecules in the sample solution
may specifically bind to, or hybridize with, one or more of the
different molecular species in one or more features of the
microarray. Following hybridization, the sample solution is removed
by washing the surface of the microarray with a buffer solution,
and the microarray is then analyzed by radiometric or optical
methods to determine to which specific features of the microarray
the labeled molecules are bound. Thus, in a single experiment, a
solution of labeled molecules can be screened for binding to
hundreds or thousands of different molecular species that together
compose the microarray. Microarrays commonly contain
oligonucleotides or complementary deoxyribonucleic molecules to
which labeled deoxyribonucleic acid and ribonucleic acid molecules
bind via sequence-specific hybridization.
[0003] Generally, radiometric or optical analysis of the microarray
produces a scanned image consisting of a two-dimensional matrix, or
grid, of pixels, each pixel having one or more intensity values
corresponding to one or more signals. Scanned images are commonly
produced electronically by optical or radiometric scanners and the
resulting two-dimensional matrix of pixels is stored in computer
memory or on a non-volatile storage device. Alternatively, analog
methods of analysis, such as photography, can be used to produce
continuous images of a microarray that can be then digitized by a
scanning device and stored in computer memory or in a computer
storage device.
[0004] Microarrays are often prepared on 1-inch by 3-inch glass
substrates, not coincidentally having dimensions of common glass
microscope slides. Commercial microarrays are often prepared on
smaller substrates that are embedded in plastic housings. FIG. 1
shows a common, currently available commercial microarray packaged
within a plastic housing. The microarray substrate 101 is embedded
within the large, rather bulky plastic housing 102 to form an upper
transparent cover over an aperture 103 within the plastic housing
102. The features that together compose the microarray are arranged
on the inner, or downward surface of the substrate 101, and are
thus exposed to a chamber within the plastic housing 102 comprising
the microarray substrate 101 and the sides of the aperture 104-107.
A transparent bottom cover may be embedded in the lower surface of
the plastic housing to seal the chamber in order to create a small
reaction vessel into which sample solutions may be introduced for
hybridization with molecular species bound to the substrate of the
microarray. Thus, the plastic housing serves to package the
microarray and protect the microarray from contamination and
mechanical damage during handling and storage and may also serve as
a reaction chamber in which sample solutions are introduced for
hybridization with features of the microarray. The plastic housing
may further serve as a support for the microarray during optical or
radiometric scanning of the microarray following exposure of the
microarray to sample solutions. Scanning may, in certain cases, be
carried out through the substrate of the microarray without a need
to remove the microarray from the plastic housing.
[0005] Although currently commonly used and widely commercially
available, the plastic microarray packaging shown in FIG. 1 has a
number of disadvantages. First, it is necessary to seal the
substrate of the microarray within the plastic housing to prevent
exchange of liquids and vapors between the external environment and
the reaction chamber formed by the substrate of the microarray, the
plastic housing, and a bottom cover. Microarray substrates are
commonly made from glass. Thus, a tight seal between the glass
microarray substrate and the plastic housing is required.
Unfortunately, many sealants used to seal glass to plastic may
contain unreactive monomer or produce reactive surfaces that
interfere chemically within the hybridization processes that need
to be carried out within the reaction vessel. A second disadvantage
is that glass and plastic exhibit different thermal expansion
behaviors, creating high stress that may lead to glass-to-plastic
bond failures during exposure of the plastic microarray packaging
and embedded microarray to thermal fluctuations. A third
disadvantage of the plastic packaging shown in FIG. 1 is that the
plastic packaging is generally insufficiently mechanically stable
to allow for reliable automated positioning of the microarray
within a scanning device. As a result, scanning devices need an
auto-focusing feature or other additional electromechanical systems
for positioning the microarray within the scanning device. A fourth
disadvantage of the plastic packaging shown in FIG. 1 is that, when
the embedded microarray is scanned without removing the microarray
from the plastic packaging, the thickness of the microarray
substrate or of the lower transparent cover, depending from which
side of the package the microarray is scanned, must have a
relatively precise and uniform thickness so that the microarray
substrate or bottom cover is not a source of uncontrolled error
during the scanning process. Manufacturing either the microarray
substrate or bottom cover to the required precision and uniformity
adds to the cost of the microarray/plastic housing module. In
general, fully automated manufacture of the plastic housing and
embedded microarray is both complex and difficult. A final
disadvantage of the plastic packaging for the microarray shown in
FIG. 1 is that the microarray/plastic housing module is primarily
designed for individual handling, and lacks features that would
facilitate automated positioning, hybridization, and scanning of
the microarray/plastic housing modules.
[0006] In order to address the above described deficiencies of the
commonly used plastic microarray housing shown in FIG. 1,
microarray strips have been developed. A microarray strip is a
linear sequence of regularly-spaced, tightly sealed reaction
chambers that each contains a precisely positioned and oriented
microarray. The microarray strip further includes tractor feed
perforations or other regularly spaced mechanical or optical
features that allow the microarray strip, and the microarray
contained within the microarray strip, to be mechanically
translated and precisely positioned within various automated
electromechanical systems. A microarray strip may also serve as a
sequence of economical and reliable storage chambers and as
packaging for storing, handling, and transporting microarrays
contained within the microarray strip. The microarray strip may be
rolled onto drums for compact and reliable storage of
microarrays.
[0007] FIG. 2 shows a microarray strip. The microarray strip 200
comprises a pocket strip 202 and cover strip 204. The microarray
strip 200 in FIG. 2 is shown during manufacture as the cover strip
204 is being laid down along the top surface of the pocket strip
202 to create sealed reaction chambers 206-207. A microarray 208
has been inserted into a pocket 210 of the pocket strip 202 which
will be next covered by the cover strip 204 during the
manufacturing process. An additional empty pocket 212, into which a
next microarray will be placed, is located to the left of pocket
210 containing microarray 208. Membrane septa 214-220 are affixed
to the cover strip 204 over corner regions of the sealed reaction
chambers 206 and 207 to provide resealable ports through which
solutions can be introduced into, and extracted from, the sealed
reaction chambers. The septa are positioned above two elongated
wells 222 and 224 formed by gaps between edges of an embedded
microarray 208 and the sides of a pocket 226 and 228. Note that
each microarray is positioned to rest on two ledges 230 (second
ledge obscured in FIG. 2) to leave a gap between the microarray and
the bottom 232 of the pocket in which the microarray is placed. The
two linear wells 222 and 224 and the gap between the bottom active
surface of the microarray and the bottom of the pocket 232 form a
single continuous volume within the pocket. The ledges 230 may be
designed so that the top surface of the microarray is flush with
the upper surface of the pocket strip 234 or, alternatively, may be
designed so that the upper surface of the microarray is recessed
within each pocket to leave a gap between the upper surface of the
microarray and the cover strip 204 following heat sealing of the
cover strip 204 to the pocket strip 202. Generally, the active
surface of the embedded microarrays, to which features are bonded,
is positioned downward, and is opposite from the side of the
microarray adjacent to the cover strip in the sealed reaction
chambers. Both edges of the pocket strip contain a linear,
regularly-spaced sequence of tractor feed perforations such as
tractor perforation 236. These perforations can be enmeshed with
gear-like feed rollers of various different mechanical systems to
allow for automated translation of the microarray strip in a
direction parallel to the length of the microarray strip and can
also provide for precise mechanical positioning of the embedded
microarrays within a scanning device.
[0008] Many types of microarray strips can be designed and
manufactured, and many different types of materials may be
employed. For example, the pocket strip and cover strip may be made
from acrylonytrile-butodiene-styrene ("ABS") plastic and can be
continuously manufactured via a vacuform process. The ABS pocket
strip and cover strip can be readily heat sealed to provide a
reasonably liquid-and-vapor-impermeable barrier. Alternatively, the
cover strip may be sealed to the pocket strip via an adhesive
sealant or may be designed to allow for mechanical sealing by
application of mechanical pressure. Alternatively, both the pocket
strip and cover strip may be manufactured from a plastic/metal foil
laminate or other materials that provide a more robust barrier to
exchange of liquid and vapor between the sealed reaction chambers
and the outside environment. The septa can be affixed either to the
upper surface or to the lower surface of the cover strip, or can be
embedded within the cover strip, and can be manufactured from many
different types of materials. One type of septa are three-ply
laminates comprising an interior elastomer layer sandwiched between
two polyester layers.
[0009] Although many of the deficiencies identified above for the
commonly available plastic microarray housing shown in FIG. 1 are
resolved by the newer microarray strip technology shown in FIG. 2,
problems can arise in microarray strips due to small gaps between
the bottom active surfaces of the microarrays and the bottoms of
the pockets that contain them. Because solution in this gap is
relatively immobilized by surface tension effects, mixing and
circulating solutions within the pockets to thoroughly expose the
active surfaces of microarrays to the solutions can be a difficult
task. One technique is to introduce air bubbles into the gaps, and
move, rotate, or shake the microarray strips to cause the bubbles
to move within the gaps. When a bubble moves within a gap, solution
is displaced, and mixing occurs. However, bubble movement within
the solution is often accompanied by laminar flow within the
solution, which, lacking vortices and other solution-mixing
phenomena, does not lead to efficient mixing and circulation. More
problematic is that the solution conformation of biopolymers can be
disrupted at air/solution interfaces, so that the presence of a
moving bubble can lead to denaturation of both solvated and bound
molecules. This technique is also difficult to apply in a
controlled manner, due to difficulties in guaranteeing
well-distributed patterns of bubble movement within the gaps. For
these reasons, designers, manufacturers, and users of microarray
strips have recognized a need for a method and system for efficient
microarray strip solution circulating and mixing.
SUMMARY OF THE INVENTION
[0010] One embodiment of the present invention is a microarray
strip pocket with roll pump features that together compose a roll
pump within the microarray strip pocket. A roll pump circulates and
mixes solution contained in the gap between the active surface of a
microarray positioned within the microarray strip pocket and the
bottom, inner surface of the microarray strip pocket. The roll pump
features include shallow and deep vertical wells that contain equal
levels of solution when the microarray strip is level. The shallow
and deep vertical wells, the gap between the active surface of a
microarray and the bottom, inner surface of the microarray strip
pocket, and a gap between the surface of an inclined feature
connecting the vertical wells and a cover strip form a continuous
volume, or space, within the reaction chamber formed when the cover
strip is bonded to the pocket strip. As the microarray strip is
rotated about an axis perpendicular to the edges of the microarray
strip and in a plane parallel to the broad surfaces of the
microarray, solution moves from the deep vertical wells into the
gap between the active surface of a microarray and the bottom,
inner surface of the microarray strip, and, as a result, solution
is displaced from the gap to the shallow vertical wells. The
displaced solution flows from the shallow vertical wells along the
inner surface of the cover strip and back to the deep vertical
wells as rotation about the axis continues. With each complete
rotation, a volume of solution determined, in part, by the height
of the solution level in the deep vertical wells passes through the
gap between the active surface of a microarray and the bottom,
inner surface of the microarray strip. By continuously rotating the
microarray strip, solution is circulated through the gap and mixed
within the gap.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] FIG. 1 shows a common, currently available commercial
microarray packaged within a plastic housing.
[0012] FIG. 2 shows a microarray strip.
[0013] FIG. 3 illustrates an empty pocket within a microarray strip
that includes roll pump features.
[0014] FIG. 4 shows the pocket illustrated in FIG. 3 following
insertion of a microarray.
[0015] FIGS. 5A-5B illustrate introduction of a sample solution
into a reaction chamber of a microarray strip that includes roll
pump features.
[0016] FIG. 6 illustrates operation of a roll pump during rotation
of a microarray strip reaction chamber.
DETAILED DESCRIPTION OF THE INVENTION
[0017] One embodiment of the present invention is a roll pump
included within a reaction chamber of a microarray strip. The roll
pump comprises features molded into the pocket, including two deep
vertical wells and two shallow vertical wells that are
interconnected with gaps below a microarray positioned within the
reaction chamber and between the wells and a cover strip that forms
the top of the reaction chamber. As the microarray strip is rotated
about a horizontal axis perpendicular to the edges of the
microarray strip, solution continuously flows from the deep
vertical wells into a gap between the active surface of a
microarray and the bottom, inner surface of the reaction chamber,
from the gap between the active surface of a microarray and the
bottom, inner surface of the reaction chamber into the shallow
vertical wells, and from the shallow vertical wells, along the
inner surface of the cover strip, back to the deep vertical wells.
The continuous flow of solution through the gap between the active
surface of a microarray and the bottom, inner surface of the
reaction chamber results in circulation and mixing of solution
within the gap, thoroughly exposing the active surface of the
microarray to the solution contained within the reaction
chamber.
[0018] FIG. 3 illustrates a pocket within a microarray strip that
includes roll pump features. The pocket 302, shown in a partial
cutaway view, includes two ledges 304 (second ledge obscured in
FIG. 3) on which the microarray substrate is placed. The pocket
additionally contains two ramp features 306 and 308 that each form
gutter dams 310 and 312. The ramp features are adjacent to two
elongated rectangular box-like features 314 and 316.
[0019] FIG. 4 shows the pocket illustrated in FIG. 3 following
insertion of a microarray. In FIG. 4, the microarray 402 has been
positioned to rest on top of the ledges (304 in FIG. 3) molded into
the sides of the pocket perpendicular to the edge 404 of the pocket
strip. The edges of the microarray 406-407 parallel to the edge of
the pocket strip 404 are flush with the interior faces of the
elongated rectangular features 316 and 314, respectively. A cover
strip can be heat sealed or otherwise fastened to the elongated
rectangular features 316 and 314 in order to prevent solution from
entering a gap between the top surface of the microarray and the
cover strip. The ramp features 306 and 308, following insertion of
the microarray, provide two vertical wells 408-409 and 410-411 on
each side of the microarray 406-407 parallel to the edge of the
pocket strip 404. The right-hand vertical wells 408 and 410 are
deeper than the shallow, left-hand vertical wells 409 and 411. The
depth of the right-hand vertical wells 408 and 410 result from
gutter dams 310 and 312, respectively. There are gaps between the
bottom surface of the microarray 406 and the bottom of the pocket
(302 in FIG. 3) and between the top of the ramp features 306 and
308 and the surface 412 of the pocket strip. Once the cover strip
is bound to the surface 412 of the pocket strip, producing an
enclosed reaction chamber around the microarray, the vertical wells
408-411, gaps below the bottom surface of the microarray and above
the gutter ramps 306-308 form a continuous volume around the
microarray substrate.
[0020] FIGS. 5A-5B illustrate introduction of a sample solution
into a reaction chamber of a microarray strip that includes roll
pump features. In FIG. 5A, a reaction chamber 502, shown in cross
section, is positioned below a sample-introducing machine 504 that
includes a pipette tube 506 and a vent tube 508. In FIG. 5B, the
sample-introducing machine 504 has been lowered towards the
reaction chamber 502 so that the pipette tube 506 has pierced the
septum 510 and cover strip 512 directly above a deep vertical well
514 and the vent tube 508 has pierced a septum 516 and a cover
strip 512 at a position directly above a shallow vertical well 518.
Sample solution 520 has flowed through the pipette tube 506 from
the sample-introducing machine 504 into the vertical well 514, and
air or liquid displaced by the introduced sample solution 520 has
been removed from the reaction chamber 502 via vent tube 508.
During automated hybridization processes, the sample-introducing
machine 504 may move back and forth between sample vessels or
microtitre plates and reaction chambers of a microarray strip
positioned via the tractor feed perforations or other alignment
features to receive a sample solution from the sample-introducing
machine.
[0021] FIG. 6 illustrates operation of the roll pump that
represents one embodiment of the present invention. The roll pump
operates when a reaction chamber that incorporates roll pump
features is rotated about an axis in a plane parallel to the plane
of the microarray and perpendicular to the edges of the pocket
strip and cover strip of the microarray strip containing the
reaction chamber. In FIG. 6, the cross-section of a reaction
chamber is shown in six orientations during rotation of the
reaction chamber about an axis 602 (shown in cross-section in FIG.
6) in the plane of the cover strip and perpendicular to the edges
of the cover strip and pocket strip. The reaction chamber in a
first position 604 is level with the cover strip 606 oriented
upward. Sample solution 608 is present in both the shallow vertical
well 610 and the deep vertical well 612 and underneath the
microarray and in contact with the active surface of the
microarray. The active surface of the microarray is represented by
dotted line 614 in FIG. 6. Sample solution is drawn into and held
in the gap between the active surface 614 of the microarray and the
bottom 616 of the reaction chamber by capillary action.
[0022] The reaction chamber is rotated counterclockwise about
horizontal rotation axis 602. At position 618, the reaction chamber
is tilted upward, with the deep vertical well 612 higher than the
shallow vertical well 610. In this orientation, the sample solution
that occupied the deeper vertical well 612 when the reaction
chamber was in the first, horizontal position 604 has, for the most
part, seeped into the gap between the active surface of the
microarray 614 and the bottom of the reaction chamber 616, with
sample solution that, in the first horizontal position 604,
previously occupied the gap between the active surface of the
microarray and the bottom of the reaction chamber, displaced by the
sample solution from the deep vertical well into the shallow
vertical well 610. Solution is prevented from flowing directly from
the deep vertical well 612 to the shallow vertical well 610 by the
gutter dam 613 formed from ramp feature 615. Note that, in the
first, horizontal position 604, equal volumes of sample solution
occupy both vertical wells 610 and 612. However, in the first
tilted position 618, only a small amount 620 of sample solution
remains in the deeper vertical well 612 while a greater amount 622
of sample solution now occupies the shallow vertical well 610. The
solution moves through the gap between the active surface of the
microarray and the bottom of the reaction chamber under
gravitational force due to the tilting of the reaction chamber.
Thus, bulk flow of solution through the gap is effected, although
the gap is completely filled with solution during rotation, held in
place by surface tension.
[0023] As rotation of the reaction chamber in a counterclockwise
direction about the horizontal rotation axis 602 continues, the
reaction chamber reaches a third, tilted and inverted position 624.
In this position, the sample solution 626 occupying the shallow
vertical well 610 is resting primarily on a side of the shallow
vertical well 628 and on the inner surface of the cover strip 606.
Note that, in the third position 624, sample solution remains in
the gap between the active surface of the microarray 614 and the
bottom of the reaction chamber 616.
[0024] As rotation continues about the horizontal axis 602 in a
counterclockwise direction, the reaction chamber reaches a fourth,
horizontal and inverted position 630. In the fourth position, the
sample solution 632, formerly pooled within the shallow vertical
well 610, is resting entirely on the inner surface of the cover
strip 606. No longer confined within the vertical well 610, the
sample solution 632 appears flattened as it spreads out across the
surface of the cover strip 606.
[0025] As rotation about the horizontal axis 602 continues in a
counterclockwise direction, the reaction chamber reaches a fifth
position 634 in which the reaction chamber remains inverted and is
tilted downward. In this fifth position 634, the droplet of sample
solution 636 that rested in the fourth position on the inner
surface of the cover strip below the inverted shallow vertical well
610, has flowed downward along the inner surface of the cover strip
606 and pooled in a wedge-shaped volume formed by a side 638 of the
deep vertical well 612 and the inner surface of the cover strip
606.
[0026] As rotation of the reaction vessel continues in a
counterclockwise direction, the reaction vessel reaches a sixth,
downward-tilted position 640. In this position, the droplet of
sample solution 642 has shifted to occupy a wedge-shaped volume
bounded by the bottom surface 644 of the deep vertical well 612 and
a side 638 of the deep vertical well.
[0027] Finally, as rotation of the reaction vessel continues in a
counterclockwise direction about the horizontal axis 602, the
reaction vessel returns to the first, level and upright position
604, described above. As the reaction chamber is rotated into this
position, pooled sample solution within the deep vertical well 612
flows into the gap between the active surface 614 of the microarray
and the bottom 616 of the reaction vessel displacing sample
solution from that gap to the shallow vertical well 610.
[0028] Thus, following a complete 360.degree. rotation of the
reaction vessel about the horizontal rotation axis 602, sample
solution has flowed from the vertical well 612 into the space
between the active surface of the microarray 614 and the bottom 616
of the reaction vessel, and displaced sample solution from that
space has been displaced into the shallow vertical well 610 and has
flowed from the shallow vertical well 610 along the inner surface
of the cover strip 606 back to the deep vertical well 612.
Continuous rotation of a reaction vessel in the fashion illustrated
in FIG. 6 produces many cycles of solution exchange between the
vertical wells 610 and 612 and the gap between the active surface
of the microarray 614 and the bottom of the reaction vessel
616.
[0029] Although the present invention has been described in terms
of a particular embodiment, it is not intended that the invention
be limited to this embodiment. Modifications within the spirit of
the invention will be apparent to those skilled in the art. For
example, many different constellations of roll pump features may be
used to create the deep and shallow vertical wells at opposite ends
of each side of the reaction chamber. In an alternate embodiment,
no gutter ramp connects the two wells. In still another embodiment,
vertical wells may be included along only one side of the reaction
vessel, rather than both sides, as shown in the described
embodiment. The sizes and shapes of the vertical wells and gap
between the active surface of the microarray and bottom of the
reaction vessel may vary considerably, and may be selected to
accommodate desired volumes of solutions in the vertical wells and
in the space between the active surface of the microarray and the
bottom of the reaction vessel. In another embodiment, only a single
vertical well at one end of the reaction chamber may be included,
with displaced sample solution simply pooling around and above the
microarray substrate at the opposite end of the reaction chamber.
In still another embodiment, two spaces at either end of the
reaction chamber, joined via the capillary gap underneath the
microarray, and a gap between the microarray and the cover strip
may constitute a roll pump. While the inclined-ramp gutter dam
feature serves, in the described embodiment, as a type of one-way
valve, or channeling mechanism, other types of one-way valves, or
channeling mechanisms, may be employed in alternate embodiments to
direct solution from one side of the reaction chamber into the
capillary gap underneath the microarray. The pocket of a microarray
strip including roll pump features may be manufactured from many
different types of materials, including synthetic polymers,
polymer/metal foil laminates, metals, ceramics, and other
materials. Because microarray strips can be conveniently rolled
onto reels, the rotation required to activate the roll pumps of
reaction chambers within a microarray strip and be applied to a
reel containing a rolled-up microarray strip. Although the
described embodiment concerned a roll pump incorporated within the
reaction chamber of a microarray strip, roll pumps within the scope
of the present invention may be employed within other types of
microarray packaging and reaction chamber systems, including
individual plastic housings. Reaction chambers enclosing other
types of reactive entities, other than microarrays, may also
include a roll pump according to the present invention. For
example, a substrate with a uniform reactive coating or surface may
be more effectively exposed to a solution via a roll pump. Finally,
a roll pump may be included within any enclosed region for
circulation of solution within the region.
[0030] The foregoing description, for purposes of explanation, used
specific nomenclature to provide a thorough understanding of the
invention. However, it will be apparent to one skilled in the art
that the specific details are not required in order to practice the
invention. The foregoing descriptions of specific embodiments of
the present invention are presented for purpose of illustration and
description. They are not intended to be exhaustive or to limit the
invention to the precise forms disclosed. Obviously many
modifications and variations are possible in view of the above
teachings. The embodiments are shown and described in order to best
explain the principles of the invention and its practical
applications, to thereby enable others skilled in the art to best
utilize the invention and various embodiments with various
modifications as are suited to the particular use contemplated. It
is intended that the scope of the invention be defined by the
following claims and their equivalents:
* * * * *