U.S. patent application number 10/346259 was filed with the patent office on 2003-06-12 for specimen plate lid and method of using.
This patent application is currently assigned to IRM LLC. Invention is credited to Burow, Kristina Marie, Caldwell, Jeremy, Downs, Robert Charles, Mainquist, James Kevin, Meyer, Andrew J., Sipes, Daniel G., Weselak, Mark Richard.
Application Number | 20030108450 10/346259 |
Document ID | / |
Family ID | 24274954 |
Filed Date | 2003-06-12 |
United States Patent
Application |
20030108450 |
Kind Code |
A1 |
Mainquist, James Kevin ; et
al. |
June 12, 2003 |
Specimen plate lid and method of using
Abstract
The specimen plate lid is generally a block, with a cover
portion and a side portion. An alignment protrusion extends from
the side portion and cooperates with an alignment member of the
specimen plate to assist in manually or roboticly guiding the lid
onto the specimen plate. An underside surface of the cover has a
sealing perimeter for receiving a seal constructed from a compliant
material, and shaped to cooperate with a complimentary sealing
surface on the specimen plate. The lid is weighted so that when the
lid is aligned and positioned on the specimen plate, the weight of
the lid provides a gravitational force to sufficiently compress the
seal against the sealing surface on the specimen plate.
Accordingly, the lid is sufficiently sealed to the specimen plate
to avoid contamination and impermissible drying.
Inventors: |
Mainquist, James Kevin; (San
Diego, CA) ; Downs, Robert Charles; (La Jolla,
CA) ; Weselak, Mark Richard; (San Diego, CA) ;
Meyer, Andrew J.; (Cardiff-by-the-Sea, CA) ; Burow,
Kristina Marie; (Chicago, IL) ; Sipes, Daniel G.;
(San Diego, CA) ; Caldwell, Jeremy;
(Cardiff-by-the-Sea, CA) |
Correspondence
Address: |
TIMOTHY L. SMITH
GENOMICS INSTITUTE OF THE
NOVARTIS RESEARCH FOUNDATION
10675 JOHN JAY HOPKINS DRIVE, SUITE E225
SAN DIEGO
CA
92121-1127
US
|
Assignee: |
IRM LLC
c/o Sophia House 48 Church Street
Hamilton
BM
|
Family ID: |
24274954 |
Appl. No.: |
10/346259 |
Filed: |
January 15, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10346259 |
Jan 15, 2003 |
|
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09569325 |
May 11, 2000 |
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6534014 |
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Current U.S.
Class: |
422/400 ;
215/230; 436/183 |
Current CPC
Class: |
B01L 3/50853
20130101 |
Class at
Publication: |
422/99 ; 422/102;
215/230; 436/183 |
International
Class: |
B01L 003/00 |
Claims
What is claimed is:
1. A lid for a specimen plate, comprising: a cover having a top
surface, a bottom surface, and a side; an alignment protrusion
extending from the side of the cover, the alignment protrusion
positioned to cooperate with an alignment member of the specimen
plate; a sealing perimeter positioned on the bottom surface of the
cover; and wherein the alignment protrusion facilitates aligning
the lid to the plate so that a seal is compressibly received
between the sealing perimeter and a sealing surface of the specimen
plate.
2. The lid according to claim 1 wherein the alignment protrusion is
a plurality of alignment tabs.
3. The lid according to claim 1 wherein the alignment member of the
specimen plate includes at least one sidewall of the specimen
plate.
4. The lid according to claim 1 wherein the seal is a perimeter
seal attached to the sealing perimeter.
5. A lid according to claim 1 wherein the seal is attached to the
sealing surface of specimen plate.
6. The lid according to claim 1 wherein the alignment protrusion is
constructed in the form of a lip.
7. The lid according to claim 1 wherein the lid is constructed from
a single block.
8. The lid according to claim 1 wherein the lid is constructed of a
heavy material to facilitate compressing the seal.
9. The lid according to claim 1 wherein the lid is constructed from
stainless steel.
10. The lid according to claim 1 wherein the cover has separate
weight members attached to the cover.
11. The lid according to claim 1 wherein the cover has a weight in
the range of about 100 grams to about 500 grams to facilitate
compressing the seal.
12. The lid according to claim 1 wherein the cover has a weight of
about 400 grams to facilitate compressing the seal.
13. The lid according to claim 1 wherein the alignment protrusion
is constructed within a tolerance of about 0.100 mm to about 0.2
mm.
14. The lid according to claim 1 wherein the seal is a contiguous
perimeter seal between the lid and specimen plate.
15. The lid according to claim 1 wherein the cover is substantially
rectangular, with a longer edge and a shorter edge, and the
alignment protrusion is constructed in the form of alignment tabs
and the alignment member are sidewalls of the specimen plate.
16. The lid according to claim 15 wherein at least one alignment
tab is positioned along each shorter edge and at least one
alignment tab is positioned along each longer edge.
17. The lid according to claim 16 wherein two alignment tabs are
positioned near the ends of each shorter edge and a single
alignment tab is positioned near the center of each longer
edge.
18. The lid according to claim 15 wherein the seal extends around a
corner of the cover by using two connected forty-five degree
angles.
19. The lid according to claim 15 wherein the alignment tabs are
constructed in the form of at least two corner tabs.
20. The lid according to claim 1 wherein the seal fits into a
groove.
21. The lid according to claim 1 wherein the seal is a perimeter
seal constructed of a highly compliant material.
22. The lid according to claim 21 wherein the perimeter seal is
constructed of a silicone rubber.
23. The lid according to claim 1 wherein the cover has a plurality
of through-holes for diffusing gas, the through-holes positioned
within an area bounded by the sealing perimeter.
24. The lid according to claim 23 wherein each through-hole is
about 1 mm in diameter.
25. The lid according to claim 1 wherein the lid further includes a
recessed area for increasing a volume of gas retained between the
cover and a top surface of the specimen plate.
26. The lid according to 25 wherein the lid further includes
through holes positioned in an area bounded by the sealing
perimeter, the through-holes constructed to keep the volume of
retained gas at an approximately 5 percent CO2 concentration.
27. The lid according to claim 1 wherein the lid further includes
an opening having a gas permeable membrane for diffusing.
28. The lid according to claim 1 wherein the lid further includes a
gripper structure for coupling with a robotic gripper.
29. The lid according to claim 28 wherein the gripper structure
includes a gripper lip positioned at an edge of the cover.
30. The lid according to claim 1 wherein the alignment protrusion
has a chamfer at a lower portion cooperating with the sidewall.
31. A method of manufacturing a lid for specimen plate, comprising:
selecting a block of a heavy metal; shaping an alignment protrusion
in the block, the alignment protrusion positioned to cooperate with
a sidewall of the specimen plate; forming a sealing perimeter in an
underside surface of the block, the sealing perimeter having a
geometry to align with a sealing surface on the specimen plate;
constructing a seal from a highly compliant material; and attaching
the seal to the sealing perimeter.
32. The method according to claim 31 wherein the sealing perimeter
is a groove and the seal is removeably fitted into the groove.
33. The method according to claim 31 further including forming a
chamfer on the alignment protrusion.
34. The method according to claim 32 wherein the alignment
protrusion is constructed in form of a plurality of alignment
tabs.
35. The method according to claim 31 wherein the block is selected
to be a stainless steel.
36. The method according to claim 31 wherein the seal is
constructed from silicone rubber.
37. The method according to claim 31 wherein the shaping step
includes casting or machining.
38. The method according to claim 31 further including shaping a
gripper structure on the lid so that a robotic gripper assembly can
couple to the lid.
39. The method according to claim 31 further including shaping a
recess into the underside of the lid to provide an increased volume
of retained gas between the lid and an upper surface of the
specimen plate.
40. The method according to claim 31, further including forming a
plurality of through-holes in the lid.
41. The method according to claim 31, further including forming an
opening in the lid and placing a gas permeable membrane in the
opening.
42. A method of using a lid to substantially seal a specimen plate,
comprising: providing a heavy lid with a plurality of alignment
tabs, the heavy lid having a seal constructed of a highly compliant
material on its underside; engaging the lid; positioning the lid
generally aligned above the specimen plate; partially lowering the
lid to the plate so that each of the alignment tabs begins to
engage a sidewall of the plate; continuing to lower the lid to the
plate, the alignment tabs facilitating the self-alignment of the
lid to the plate so that the seal contacts and cooperates with a
sealing surface on the plate; disengaging the lid, so that the lid
rests on the specimen plate; and compressibly receiving the sealing
surface against the seal.
43. The method according to claim 42 wherein the engaging step
includes coupling a robotic gripper attachment to the lid.
44. The method according to claim 42 wherein the partially lowering
step includes engaging a chamfered surface on each alignment
tab.
45. An automated robotic lidding system, comprising: a lid for a
specimen plate; a gripping structure on the lid; a plurality of
alignment tabs on the lid, each alignment tab being positioned to
cooperate with a sidewall of the specimen plate; a robot having a
gripping attachment for coupling with the gripping structure on the
lid; a compliant seal on the underside of the lid, the seal
positioned to contact and cooperate with a sealing surface on the
specimen plate; and wherein when the robot rests the lid on the
specimen plate, the weight of the lid compresses the compliant seal
against the sealing surface of the specimen plate.
46. A lid for a specimen plate, comprising: a cover having a top
surface, a bottom surface, and a side; an alignment protrusion
extending from the side of the cover, the alignment protrusion
positioned to precisely cooperate with a sidewall of the specimen
plate; a sealing perimeter on the bottom surface of the cover; and
wherein the alignment protrusion facilitates aligning the sealing
perimeter to a sealing area on the plate, the cover being precisely
positioned so that the sealing perimeter does not touch any sample
well on the specimen plate.
47. A lid for a specimen plate, comprising: a cover having a top
surface, a bottom surface, and a side; a seal positioned on the
bottom surface of the cover; and wherein the lid rests on the plate
so that the seal is compressibly received against a sealing surface
on the specimen plate.
48. A lid for a specimen plate, comprising: a metal cover having a
top surface, a bottom surface, and a side; and wherein the lid
rests on the plate so that the lid is compressibly received against
a sealing surface on the specimen plate.
49. A system using a lid to substantially seal a specimen plate,
comprising: means for providing a heavy lid with a plurality of
alignment tabs, the heavy lid having a seal constructed of a highly
compliant material on its underside; means for engaging the lid;
means for positioning the lid generally aligned above the specimen
plate; means for partially lowering the lid to the plate so that
each of the alignment tabs begin to engage a sidewall of the plate;
means for continuing to lower the lid to the plate, the alignment
tabs facilitating the self-alignment of the lid to the plate so
that the seal contacts and cooperates with a sealing surface on the
plate; means for disengaging the lid, so that the lid rests on the
specimen plate; and wherein the seal is compressibly received
against the sealing surface.
Description
FIELD OF THE INVENTION
[0001] The field of the present invention is the manufacture and
use of lids for containers. More particularly, the present
invention relates to lids for use on specimen plates, such as
microplates.
BACKGROUND OF THE INVENTION
[0002] Specimen plates are used in several industries, such as the
biotechnology and biomedical industries. The specimen plates can be
used, for example, to hold multiple compounds or materials, to
conduct multiple assays on one or more compounds, to facilitate
high throughput screening and to accelerate the production and
testing of a large number of samples. For the purpose of this
discussion, the term "specimen" or "sample" refers to chemicals,
assays, reagents, genetic material, biological compounds, or
therapeutic material, in any form, such as a liquid, gel, or solid
form.
[0003] Typically a specimen plate has multiple sample wells on its
top surface into which one or more specimen can be placed, although
a particular sample plate may have only a single well for the
entire plate. Each of the wells forms a container into which a
specimen is placed. The specimen plate also can be heated, cooled,
or shaken to facilitate a desired process. Specimen plates are
configured to meet industry standards. For example, some commonly
used standard plates have 96, 384, or 1536 wells. Other sample
plates are configured with 1, 2, 4, 6, 12, 24 or 48 wells. Such
plates are available from, for example, Greiner America Corp., P.
O. Box 953279, Lake Mary, Fla. 32795-3279. Plates may be handled
manually or robotically.
[0004] It is known to use specimen plates in conjunction with
automated processing equipment, such as high throughput screening
equipment. Automated equipment, such as automated liquid
dispensers, can receive appropriately configured specimen plates
and deposit samples or reagents into the plate wells. Other known
automated equipment facilitates the processing and testing of
specimens using loaded specimen plates.
[0005] It is also known to provide a lid to cover a specimen plate.
This is desirable in some applications. For example, the samples in
the wells may need to incubate, or it may be desired to store the
samples for an extended period of time. By covering the wells,
contamination and evaporation may be reduced. Wells located near
the edges of some known sample plates also can be prone to
increased evaporation relative to middle wells when covered by a
lid. This phenomena is often referred to as an "Edge Effect." Such
sample plates suffer a deficiency of non-uniform drying, which may
cause inaccuracy in testing or assay procedures or other
inefficiencies in automated processes.
[0006] It is known to cover a sample plate manually, such as by
positioning a plastic lid over the top of the specimen plate. One
such plastic lid is Model No. 656191 from Greiner America Corp., P.
O. Box 953279, Lake Mary, Fla. 32795-3279. Such plastic lids suffer
a deficiency in that it is difficult to form an air tight seal
between the lid and specimen plate, leading to evaporation and the
possibility of contamination. One known way to reduce those effects
is to adhere tape around the edges of the plastic lid to seal the
plastic lid to the plate. This makes access to the wells difficult
in that the tape needs to be removed to gain access. In addition,
adhesive residue can remain on the edges of the plate and lid,
leading to the possibility of further contamination or difficulty
in handling. Moreover, this covering and uncovering process is
relatively time consuming and requires some manual dexterity.
Substantial handling of the specimen plate is also required, which
may undesirably agitate the contents of the wells and lead to
inaccurate results. Alternatively, a foil tape can be applied
directly to the top of the wells. Such foil tape also suffers from
being time consuming to apply, increased contamination risk, and
undue agitation.
[0007] Accordingly, there is a need for a specimen plate lid that
provides enhanced sealing and provides increased efficiency in
placement on a specimen plate or removal from a specimen plate.
Further, there is a need for a specimen plate with improved gas
exchange characteristics.
SUMMARY OF THE INVENTION
[0008] The present invention alleviates to a great extent the
disadvantages of the known specimen plate lids and methods of using
them by providing a specimen plate lid having a seal between a
lower surface of the lid and a mating upper surface of a specimen
plate. Generally, the lid includes a plate member having an
exterior surface that is exposed when placed on a specimen plate,
and an lower/inner surface that faces the specimen plate when
placed on top of the specimen plate. Preferably a side portion
extends from the periphery of the lower/inner surface so that the
side portion overlaps with side surfaces of the specimen plate when
the lid is placed over the specimen plate. The side portion has an
exterior surface that is exposed and an inner surface facing the
specimen plate when the lid is placed over the specimen plate.
[0009] Alignment tabs preferably are located on the side portion
and cooperative mating elements are located on the specimen plate
to assist in guiding the lid onto the specimen plate and in
providing a desired registration with the specimen plate. The lower
surface of the lid has a sealing perimeter constructed to cooperate
with a complimentary sealing surface on the specimen plate. A seal
formed from a compliant sealing material is positioned between the
lower surface of the lid and the specimen plate. The seal is shaped
to cooperate with both the sealing perimeter on the lid and the
complimentary sealing surface on the specimen plate. Preferably
seal retaining members are provided on the sealing perimeter of the
lid to retain the seal in place. The lid also preferably has
sufficient weight to compress the seal when the lid is aligned and
positioned on the specimen plate. In this way, the weight of the
lid provides a gravitational force sufficient to compress the seal
against the sealing surface on the specimen plate, enhancing the
level of diffusion resistance.
[0010] It is an advantage of the present invention that the
specimen plate lid can be accurately and relatively efficiently
positioned on a specimen plate. Since the lid and its compressible
seal alone provide a good barrier between the specimen plate wells
and the outside environment, additional mechanical or adhesive
sealing is not required. This saves material and also can reduce
the time required to cover and seal a specimen plate. Moreover,
agitation and other disturbance of the specimen material in the
wells can be minimized.
[0011] It is a further advantage that the specimen plate lid is
well suited for handling by a robotic material handling system. For
example, the lid is generally self-aligning, permitting the lid to
be easily positioned by robotic handling. Additionally, since the
lid is self-sealing with the specimen plate, operator intervention
is not required to mechanically seal the plate.
[0012] These and other features and advantages of the present
invention will be appreciated from review of the following detailed
description of the invention, along with the accompanying figures
in which like reference numerals refer to like parts
throughout.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] FIG. 1 is a perspective view of a specimen plate lid and
specimen plate in accordance with the present invention;
[0014] FIG. 2 is a perspective view of an inner surface of a
specimen plate lid in accordance with the present invention;
[0015] FIG. 3 is a bottom plan view of a specimen plate lid in
accordance with the present invention;
[0016] FIG. 4 is a side view of a specimen plate lid in accordance
with the present invention;
[0017] FIG. 5 is another side view of a specimen plate lid in
accordance with the present invention;
[0018] FIG. 6 is a fragmentary side view of a portion of a specimen
plate lid in accordance with the present invention;
[0019] FIG. 7 is a fragmentary side view of a portion of a specimen
plate lid in accordance with the present invention;
[0020] FIG. 8 is a cross-sectional view of an example of a
compliant seal in accordance with the present invention;
[0021] FIG. 9 is a bottom plan view of an alternative embodiment of
a specimen plate lid in accordance with the present invention;
[0022] FIG. 10 is a side view of the specimen plate illustrated in
FIG. 9;
[0023] FIG. 11 is another side view of the specimen plate lid
illustrated in FIG. 9;
[0024] FIG. 12 is a fragmentary side view of a portion of the
specimen plate lid illustrated in FIG. 9;
[0025] FIG. 13 is a fragmentary side view of another portion of the
specimen plate lid illustrated in FIG.9;
[0026] FIG. 14 is a fragmentary perspective view of a specimen
plate lid in accordance with the present invention;
[0027] FIG. 15 is a cross-sectional view of a groove and seal in a
specimen plate lid in accordance with the present invention, with a
sealing surface of the specimen plate positioned near an edge of
the seal;
[0028] FIG. 16 shows the lid of FIG. 15 with the sealing surface of
the specimen plate positioned near the center of the seal;
[0029] FIG. 17 illustrates an example of a robotic transport system
and a specimen plate lid in accordance with the present
invention;
[0030] FIG. 18 is a flowchart of a method of manufacturing a
specimen plate lid in accordance with the present invention;
[0031] FIG. 19 is a flowchart of a method of using a specimen place
lid made in accordance with the present invention;
[0032] FIG. 20 is a flowchart of a method of manufacturing and
using a specimen plate lid in accordance with the present
invention; and
[0033] FIG. 21 is a partial cross-section view of a specimen plate
lid made in accordance with the present invention.
DETAILED DESCRIPTION OF THE INVENTION
[0034] In accordance with the present invention, a specimen plate
lid is provided. Referring now to FIGS. 1-7, there is shown a
specimen plate lid 10 made in accordance with the present
invention. Specimen plate lid 10 is generally a block having a
cover portion 12 and side portions 13. The cover 12 has an x-axis
edges 14 and a y-axis edges 16. An alignment protrusion in the form
of two alignment tabs, or legs, 18 are positioned along each y-axis
edge 16 while one x-axis alignment tab, or leg, 19 is positioned on
each x-axis edge 14. It will be appreciated that other numbers and
positions of alignment tabs can be used depending upon the size and
shape of the specimen plate. Further, it will be appreciated that
the alignment protrusion can take alternative forms, such as a lip,
pins, a curtain, or corner tabs.
[0035] The y-axis alignment tabs 18 are positioned spaced apart and
near the ends of each y-axis edge 16. Each x-axis alignment tab 19
is positioned approximately centered on each corresponding x-axis
edge 14. It will be appreciated that the alignment tabs may be
positioned at different locations adjacent the edges of the
specimen plate lid 10.
[0036] The specimen plate 25 is also generally a block having a
sample area 29 and sidewalls 27. The sample area 29 includes many
sample wells such as exterior well 31 and interior well 32. A
perimeter surface 33 is positioned at the top of the sidewalls 27
and surrounds the sample area 29. It will be appreciated that
although the surface area 33 is shown as substantially a
rectangular frame, other shapes and geometries are contemplated. At
the bottom edge of sidewall 27 is a registration edge 23.
Registration edge 23 facilitates the efficient positioning in
automated equipment.
[0037] In use, the specimen plate lid is placed on the specimen
plate 25 to cover and sufficiently seal the wells. To facilitate
the gentle and efficient covering and uncovering of the specimen
plate, the alignment tabs on lid do not frictionally mate with the
sidewalls of the specimen plate. Instead, the alignment tabs are
constructed to cooperate with the sidewalls of the plate and to
guide the lid to the specimen plate, but have sufficient spacing so
that the tabs do not frictionally engage the sidewalls of the
specimen plate.
[0038] To precisely position the lid, the alignment tabs are
constructed with a tolerance of about 0.13 mm. It will be
appreciated that other tolerances can be used to precisely place
the lid on the specimen plate. Such precise positioning permits the
seal to be compressed without the seal touching any sample
well.
[0039] To cover the sample area of the specimen plate, the lid 10
is lifted and positioned above the sample area 29 of the specimen
plate 25. It will be appreciated that the lifting and positioning
may be performed manually or by a machine such as a robot. The
specimen plate lid 10 is generally aligned with the specimen plate
25 and lowered. As the cover 12 is lowered, the alignment tabs 18,
19 begin to cooperate with the sidewalls 27 on the specimen plate.
Optionally, each of the alignment tabs 18, 19 has a chamfer 39 at
its lower portion to facilitate self-aligning the lid 10 to the
plate 25. With the alignment tabs chamfered, the alignment tabs
more readily engage the sidewalls of the plate, but accurately
position the lid as the lid is lowered. In such a manner, the cover
12 can be only approximately positioned above the sample area 29
and as the cover 12 is lowered, the chamfered alignment tabs 18, 19
guide and align the cover 12. Thereby, when the cover 12 is fully
resting on the specimen plate, the cover 12 is precisely positioned
and aligned with the specimen plate 25.
[0040] Referring now to FIG. 2 the underside of cover 12 is shown
to have a sealing perimeter constructed as a groove 43 adjacent the
perimeter of the cover 12. The groove 43 provides a sealing area on
the lid and is positioned such that when the cover 12 is positioned
on the specimen plate 25, the groove 43 aligns approximately in the
center of the perimeter surface 33 of the specimen plate 25. It
will be appreciated that a sealing area may be provided on the lid
in other ways, such as providing a flat surface for adhering a
seal. It will also be appreciated that the seal could be attached
to the specimen plate and positioned to cooperate with a sealing
perimeter on the lid.
[0041] In the disclosed example, a rubber seal 37 is fittingly
retained in the groove 43. It will be appreciated that other
methods such as adhering may be used to fix the seal 37 in the
groove 43. However, a frictional fit is preferred as the seal 37
may be conveniently removed for cleaning, replacement, or
sterilization. The seal 37 is preferably a rubber, and most
preferably a silicon rubber. Silicon rubber, or another highly
compliant material, is preferred as an efficient seal can be
created with a minimum compressive force.
[0042] With the seal 37 constructed from a highly compliant
material and fittingly positioned in the groove 43, when the cover
12 is fit onto the specimen plate 25, the seal 37 is compressed by
the weight of the lid to the perimeter surface 33. The perimeter
surface 33 is a sealing surface for compressibly receiving the seal
37.
[0043] In a preferred configuration, the specimen plate lid 10 is
constructed as a single piece machined from a stainless steel
block. Stainless steel is a preferred material as not only does
stainless steel have superior sterilization characteristics, but
stainless steel is also a heavy material. By constructing the
specimen plate lid 10 from a heavy material, sufficient
gravitational forces act to compress the cover 12 towards the
specimen plate 25. In such a manner the seal 37 is sufficiently
compressed to the sealing surface 33 to create a seal that provides
a barrier against contamination and evaporation. Those skilled in
the art will recognize that the specimen plate lid 10 can be
weighted using other means, such as adding weights to the cover 12
or tabs 18, 19 or constructing the lid 10 from an alternate heavy
material. To sufficiently compress the compliant seal, preferably
the lid weighs between about 100 grams and about 500 grams. Most
preferably, the lid weighs about 400 grams. It will be appreciated
that the disclosed weight range is for a standard size specimen
plate using a silicon rubber seal. Other weights may be used for
other size plates and other compliant seals. Further, some
applications may not require such complete sealing and may
sufficiently seal with less weight.
[0044] Stainless steel is also a preferred material because of its
superior machining characteristics. Due to the geometry and
narrowness of the perimeter surface 33, it is important that the
cover 12 be accurately positioned and aligned with the specimen
plate 25. By machining the alignment tabs 18, 19, the tabs can be
accurately located to within 0.100 millimeter tolerance. Further,
for efficient sealing, the underside of the cover 12 needs to be
substantially flat. Again, by machining, flatness can be assured to
within 0.100 millimeter tolerance. Although the preferred example
machines the specimen plate lid from a solid block of stainless
steel, it will be appreciated that a stainless steel piece could be
cast roughly in the shape of the specimen plate lid, and then
selected surfaces machined as required. Further, it will be
appreciated that other materials could be substituted, such as
aluminum. Although the described example uses a lid formed from a
single block, it will be appreciated that the lid may be
constructed from component parts.
[0045] Optionally, the specimen plate lid 10 may include a bar code
35 positioned at one end, and a bar code 36 placed at the other
end. The indicia on each bar code 35, 36 identifies the particular
specimen plate lid, but each bar codes has an indicia that
facilities identifying which end of the lid is being scanned. For
example, bar code 35 may be an even code while bar code 36 is an
odd code. Therefore, an automated machine can read the bar code 35,
36 and know whether a front end or a rear end of the lid is being
inserted into the machine. In a similar manner, bar codes can be
positioned on the specimen plate 25 to identify which end of the
specimen plate is being inserted into a machine. If both the lid
and the specimen plate have bar codes, then the system can assure
that the lid is positioned in the same orientation on the specimen
plate.
[0046] The specimen plate lid 10 may be used as described for
manual use. In such a manner, a technician or other operator
manually grabs, aligns, and lowers the specimen plate lid 10 over
the specimen plate 25. In a similar manner, the technician or user
would remove the specimen plate lid 10. However, it may be
desirable for some applications that the specimen plate lid 10 be
fitted and removed by an automatic system, such as a robotic
system. To facilitate manipulation by an automatic robotic system,
the specimen plate lid 10 can optionally include a gripper lip 21
on the x-axis edges 14. It will be appreciated that other
structures may be positioned on the specimen plate lid 10 for
cooperating with a gripper mechanism on a robotic system.
[0047] In use by robotic system, first a gripper portion of a
robotic member would cooperate or couple with one or both gripper
lips 21. The robotic member would then approximately position the
specimen plate lid 10 above the sample area 29. The robotic member
would lower the cover 12 until the alignment tabs 18, 19 begin
contacting the sidewalls 27 of the specimen plate 25. As the cover
12 is lowered, the robotic member preferably allows the cover 12 to
adjust and self-align to the sidewalls 27 of the specimen plate 25.
After the cover 12 is fully lowered, the gripper portion of the
robotic member can release the gripper lips 21 and the robotic
member can be retracted. The robotic member may also include a bar
code reader for reading bar code 35, 36 for identifying the lid or
specimen plate, and determining which side of the lid or plate is
leading.
[0048] Referring now to FIG. 8, a seal 37 is shown for use on the
lid 10. The seal 37 has sidewalls 55 which are fittingly received
into the groove 43. The seal 37 has two ridges 49 and a recess 51
configured to more evenly distribute a load received on the seal
37. The seal 37 also has a lip 53 which extends over the perimeter
surface 33. Therefore, as the lid 10 is lowered onto the specimen
plate 25, the load-bearing surface 54 contacts the perimeter
surface 33 and is compressed thereto as the lid is fully
lowered.
[0049] In the described example of the specimen plate 25, the
sample area 29 is substantially planer with the perimeter surface
33. Therefore, a minimum volume of air 45, or other gas, is
retained between the cover 12 and the sample area 29 when the lid
is resting on the plate. The volume 45 of gas retained is directly
proportional to the thickness of the seal 37, and more particularly
on the thickness of the lip 53. Therefore, by minimizing the
thickness of lip 53, the volume of air or other gas entrapped as a
volume when the lid is in place is minimized.
[0050] Such a minimum volume of retained gas is desired in some
applications as moisture from within the wells can be evaporated
into the retained volume 45. For example, if the samples are to be
stored for an extended period, it may be desirable to reduce
evaporation. By reducing the retained volume 45, drying effects are
minimized. Such drying effects can be particularly severe in the
exterior wells such as exterior well 31 that are near the outside
perimeter of the sample area 29.
[0051] Although a particular geometry has been shown for seal 37,
it will be appreciated that other seals constructed from a highly
compliant material can be substituted. Further, it will be
appreciated that other shapes, with or without a lip, can be used
to provide a sufficient seal between the cover 12 and the specimen
plate 25. Further, the geometry and shape of the perimeter area 33
or other sealing area may direct modification in the seal shape and
geometry.
[0052] Referring to FIGS. 9-13, another example of a specimen plate
lid 60 is shown. Specimen plate lid 60 is similar to specimen plate
lid 10, with the similar aspects only briefly addressed. Specimen
plate lid 60 has a cover 62 and sidewalls, with an alignment
protrusion constructed as alignment tabs 64 extending therefrom. As
with alignment tabs 18, 19 alignment tabs 64 have a chamfer 65 for
facilitating efficient alignment and positioning. Cover 62
optionally has a gripper lip 79 for cooperating with a robotic
member.
[0053] Specimen plate lid 60 is constructed such that when the
specimen plate lid 60 is resting on a corresponding specimen plate,
a more substantial volume 83 of gas is retained between the cover
62 and the sample area of the specimen plate. Such a substantial
volume 83 of gas is desirable, for example in an assay specimen
plate. In an assay specimen plate, it is desired that gas in the
volume space 83 interact with the wells in the specimen plate. The
wells may contain, for example, live cells that need oxygen,
humidity, N2, and CO2 to survive. However, it is important that the
gases interact with the wells in a uniform and consistent manner.
Such uniformity and consistency is difficult to achieve as the
wells have different evaporative characteristics closer to the
perimeter than the wells more towards the center of the sample
area.
[0054] In some applications, it is desired that outside gases
diffuse and mix with the gases in the retained volume 83.
Accordingly, the cover 62 of the assay plate lid 60 may be provided
with a series of small holes 67. In a preferred embodiment, each
hole 67 is approximately 1 millimeter in diameter. It will be
appreciated that other sized holes may be substituted depending
upon specific applications. Also, in the disclosed example 16 holes
are positioned in a grid pattern such that each hole is placed an
x-axis distance 75 from an adjacent hole and a y-axis distance 76
from an adjacent hole. The x-axis edge distance 77 is substantially
the same from each outer hole to the x-axis edge, and the y-axis
edge distance 78 is substantially the same from the outside holes
to the y-axis edge. It will be appreciated that other numbers and
spacings of holes may be used. Alternatively, the cover can be
constructed with a semi-permeable gas membrane in an opening. The
membrane can be a single pane, or can be constructed in multiple
panes in multiple openings arranged in the cover. By selecting the
membrane's pemeability, size and placement, the gas difference
characteristic of the assay lid can be adjusted.
[0055] Even though the cover 62 has through-holes permitting the
diffusion of gas into the volume area 83, it has been found to be
desirable that the cover 62 still be constructed to sufficiently
seal to the specimen plate 25. Without such sealing, the wells near
the perimeter of the sample area are found to impermissibly dry due
to excess evaporation, and gas diffusion to the exterior wells is
not uniform. Accordingly, the underside of cover 62 has a groove 73
and a seal 71 similar to the groove and seal already discussed.
[0056] In use, the assay plate lid 60 is fittingly positioned on a
specimen plate, and the lid and plate assembly typically placed in
an enclosed chamber. The enclosed chamber contains a desirable gas
or a gaseous mixture. For example, the chamber may be filled with
oxygen. With the lid and plate assembly in the chamber, the oxygen
enters the volume 83 and mixes with the gas in the chamber 83 and
diffuse and react with substances in the well of the plate.
[0057] Even though it is sometimes desirable that the ambient gas
mix with the gas in the volume 83 and react with the material in
the well, it is also desirable that the material in the well not
impermissibly dry. For example, each time the lid is fitted to the
specimen plate, the moisture or solvent in each well evaporates
until the moisture in the volume 83 establishes an equilibrium.
Therefore, the gas exchanged with the ambient gas must be carefully
controlled to avoid impermissible drying. Accordingly, the size and
spacing of the through-holes is selected to control gas diffusion
and drying effects.
[0058] Referring now to FIG. 12, the volume 83 is obtained by
providing a recess 81 in the underside of the cover 62.
Accordingly, the size of the recess 81 is directly proportional to
the retained volume of gas 83. In a preferred embodiment, the
recess 81 is machined from the solid stainless steel block
comprising the lid 60. It will be appreciated that other methods of
obtaining the recess may be used. A ridge 85 remains between the
groove 73 and the recess 81. The ridge 85 supports the seal lip 84
of the seal 71 when the seal 71 is compressed against the perimeter
area on the specimen plate.
[0059] The specimen plates described thus far have a perimeter area
functioning as a sealing area for compressibly receiving a seal.
However, other available specimen plates do not provide a perimeter
surface, but instead provide a more narrow plate sidewall 98 as
shown in FIGS. 14-16. In such a manner, a soft compliant seal 92
compressibly receives a top surface of the plate sidewall 98.
Accordingly, the top surface of sidewall functions as a sealing
surface.
[0060] The seal 92 is most preferably constructed of a silicon
rubber, but other highly compliant materials could be substituted.
The seal 92 is fittingly received into a groove 93. Due to
tolerances in the lid 90 or the positioning of the plate sidewall
98, the plate sidewall 98 may not always be received at the same
position in the seal 92. For example, FIG. 16 shows that the top
surface of the plate sidewall 98 may be received near the center of
the seal 92, whereas in FIG. 15 the top surface of the plate
sidewall 98 is received at an outer edge of the seal 92.
[0061] Specimen plate lid 90 has alignment tabs or legs 91, each
having a chamfer surface 97. The chamfer surface 97 assists in
aligning the plate sidewall 98 with the seal 92. The specimen plate
lid 90 is an assay plate lid having a volume 101 of gas retained
beneath the lid. As with plate lid 60 described above, specimen
plate lid 90 has a ridge 102. The ridge 102 provides lateral
support to the seal 92.
[0062] FIG. 14 shows an example corner construction for the
specimen plate lid 90. For particular specimen plates, the plate
sidewall 98 may be constructed to traverse corners using two
45-degree angles instead of a single 90-degree corner. Such a
corner configuration is not only efficient to manufacture, but
provides superior support as compared to a 90-degree angle. Since
the plate sidewall 98 is narrow, the groove 93 in the cover 94 also
needs to extend across comers using two 45-degree angles 96. In
such a manner the plate sidewall 98 more accurately cooperates with
the seal 92.
[0063] Referring now to FIG. 17, a robotic system 105 is shown
operating in accordance with the present invention. The robotic
system 105 has a robot 107 with a robotic arm 108. A gripper
attachment 109 is positioned at the end of the robotic arm 108. The
robotic system also includes one or more work stations, such as
workstation 106. The workstation may be, for example, a holding
station, a shaker station, an optical reader station, or an
automated dispensing station.
[0064] The workstation 106 has a holding area 110. Both the
workstation 106 and the gripper attachment 109 of the robot 107
have access to the holding area 110. A specimen plate 111 is shown
in an uncovered arrangement in FIG. 17. The specimen plate has a
registration lip 115 that assists in positioning the specimen plate
with the workstation 106. Alternatively, the registration lip 115
may be configured to couple with the gripper attachment so that the
robot can move and position the plate 111.
[0065] The specimen plate 112 lid has a gripper attachment
structure in the form of a pair of gripper lips 114 positioned on
each of the lid's x-axis edges. The robotic gripper attachment 109
is configured to removeably couple with the gripper lips 114. In
such a manner, the robot 107 is able to couple with the lid 112,
and lift and position the lid according to the needs of an
automated process. It will be appreciated that other gripper
attachment structures can be used according to application
requirements.
[0066] The specimen plate lid 112 also has an alignment protrusion
in the form of alignment tabs 113 for cooperating with sidewalls of
the plate 111. As the robotic arm 108 lowers the lid 112, the tabs
113 begin to engage the sidewalls. As the robot 107 further lowers
the lid, the robotic arm 108 and gripper attachment 109 permit the
lid to self-align with the plate 111. When the lid is fully resting
on the plate 111, the gripper attachment disengages and the robotic
arm 108 moves away from the workstation 106. Optionally, the
robotic system can include a barcode reader 116 for reading a
barcode on the lid or the plate for properly identifying plates or
lids. Although the barcode reader 116 is shown on the robotic arm,
it will be appreciated that the barcode reader can be placed in
other locations.
[0067] Referring now to FIG. 18, a method of manufacturing 120 a
specimen plate lid is shown in accordance with the present
invention. Block 120 shows that an initial step is to select the
proper material for the lid and the proper material for the seal.
As described above, the lid is preferably made from a stainless
steel block. However, it will be appreciated that other materials
or constructions can be used to provide sufficient weight. Further,
it will be understood that a lighter material can be selected and
weights added to the lid during construction. As already described,
the seal is preferably constructed from a highly compliant rubber
such as a silicon rubber. However, it will be appreciated that
other materials can be substituted.
[0068] The block is preferably formed into the general shape of the
lid by machining as shown in block 124. However, it will be
appreciated that the member can be generally shaped using other
methods such as casting. Alignment tabs, or legs, are positioned on
the lid such that the alignment tabs will align and cooperate with
at least three sidewalls of a specimen plate as shown in block 126.
The tabs are preferably formed with a tolerance in the range of
about 0.100 mm to about 0.2 mm, thus providing an accurate
positioning of the lid on the specimen plate. Accordingly, the seal
will not contact any wells on the sample plate. It will be
understood that the number and position of the alignment protrusion
or alignment tabs may be adjusted according to specific
applications.
[0069] In block 128 the tabs are precisely positioned on the lid to
guide the lid to the specimen plate. In a disclosed example, such
precise positioning is accomplished by machining the alignment
tabs. It will be appreciated that other methods can be used to
attach and position the alignment tabs. Chamfers are formed on the
lower portion of the alignment tabs as shown in block 130. The
chamfers facilitate self-aligning the lid to the specimen
plate.
[0070] A groove is formed on the underside of the lid as shown in
block 132. The groove is shaped and has a geometry that cooperates
with a sealing area on the specimen plate. The sealing area the
specimen plate may be, for example, a surface area or may be a
plate edge. It will be appreciated that depending upon the specific
specimen plate to be mated with, the sealing area may be shaped to
precisely mate with the sealing surface on the specimen plate or
may accommodate greater tolerances.
[0071] Block 134 shows that the seal is constructed from a highly
compliant material, and in block 136 the seal is positioned on the
sealing area. It will be appreciated that the sealing area may
include a groove for fittingly receiving the seal, or the seal may
be attached to the sealing area using another method.
[0072] Block 137 shows that a gripper attachment structure
optionally may be formed on the lid. For example, the gripper
attachment structure may be a gripper lip for coupling with a
gripper attachment on a robotic arm. In Block 138 an optional
recess may be formed in the lid to increase the volume of the
retaining gas when the lid is in place on the specimen plate. In
such a manner, the lid functions as an assay lid. In the preferred
embodiment, the recess is formed by machining the stainless steel
block. However, it will be appreciated that the recess may be
formed using other methods.
[0073] Optionally, as shown in block 139, a plurality of holes may
be formed in the lid. It will be appreciated that the size and
specific location of the holes may be adjusted for specific
applications. As described earlier, the holes function to allow gas
to diffuse into the retained gas volume.
[0074] Referring now to FIG. 19, a method of using 140 a specimen
plate is shown in accordance with the present invention. Block 143
provides a lid with alignment tabs, a seal, and a lifting
structure. In block 145, the lifting structure is engaged to lift
the lid. The lid is then generally positioned above the sample area
of the sample plate as shown in block 147. In block 149, the lid is
partially lowered toward the specimen plate, thereby permitting the
alignment tabs to begin to cooperate and engage the sidewalls on
the specimen plate. As the lid is further lowered, the alignment
tabs adjust the position of the lid to self-align the lid to the
specimen plate as shown in block 151. Once the lid is resting on
the specimen plate, the lifting structure is disengaged as shown in
block 153.
[0075] The lid may be constructed to be lifted and fitted either
manually or by robotic means. Accordingly, the lid may include
lifting structures for mating with a gripper portion of a robotic
system, such as a gripper arm. The lid may therefore have a gripper
structure such as a gripper lip as described earlier. It will be
appreciated that other types of gripper structures may be provided
on the lid depending on specific application.
[0076] Referring now to FIG. 20, a method of sealing 160 a specimen
plate is shown. Block 163 shows that a lid is constructed to be
heavy and with alignment tabs extending from the lid. In block 165,
a sealing area is identified on the underside of the lid. The
sealing area is selected to cooperate with a sealing surface on a
specimen plate. For example, the sealing surface on the specimen
plate may be a flat sealing area, or may be a plate edge as
described earlier. It will be appreciated that the sealing area may
be selected with varying geometries and positions according to
specific applications.
[0077] In block 167, a seal is constructed from a highly compliant
material. As described earlier, the highly compliant material may
be a rubber material such as a silicon rubber or plastic. It will
be appreciated that other materials can be substituted. The
compliant seal is positioned in the seal area on the underside of
the lid as shown in block 169.
[0078] The lid is then lowered toward the specimen plate so that
the alignment tabs engage sidewalls on the specimen plate, thereby
facilitating the alignment of the sealing area and the sealing
surface. When the lid is fully lowered and resting on the specimen
plate as shown in block 173, the lid is fitted to the specimen
plate. With the lid fitted to the specimen plate, the weight of the
lid compresses the compliant seal against the sealing surface as
shown in block 175. Thereby the specimen plate is sufficiently
sealed against contamination and impermissible evaporation as shown
in block 177.
[0079] FIG. 21 shows a specimen plate lid 180 sealing the perimeter
181 of a specimen plate 183. The lid 180 has an alignment tab 185
with a chamfered surface 187 for facilitating the engagement of the
sidewall 189 of the specimen plate 183. The lid 180 has a perimeter
groove 190 fittingly receiving a compliant rubber seal 191. The lid
180 has sufficient weight that when resting on the plate 183, the
leg 189 of the real 191 is compressed against the perimeter 181 of
the plate 183. Accordingly, the internal volume 195 under the cover
197 is sealed against impermissible evaporation and contamination.
The lid may be positioned such that the alignment tab 185 is
positioned against the plate sidewall 189, as shown in FIG. 21a, or
may be positioned away a distance 198 as shown in FIG. 21b. Either
way, the seal 191 is positioned in the lid 180 so that the leg 193
of the seal 191 does not contact any sample well, such as perimeter
sample well 196. In such a manner, the seal avoids contaminating
any sample well and facilitates reduced edge effects and more even
gas diffusion.
[0080] One skilled in the art will appreciate that the present
invention can be practiced by other than the preferred embodiments
which are presented in this description for purposes of
illustration and not of limitation, and the present invention is
limited only by the claims which follow. It is noted that
equivalents for the particular embodiments discussed in this
description may practice the invention as well.
Reference characters
[0081] 10 compound plate lid 73 groove
[0082] 12 cover 75 x-axis distance
[0083] 13 sides 76 y axis distance
[0084] 14 X axis edge 77 x axis edge distance
[0085] 16 y axis edge 78 y axis edge distance
[0086] 18 y axis alignment tabs 79 Gripper lip
[0087] 19 x-axis alignment tabs 81 recess
[0088] 21 Gripper lip 83 volume
[0089] 23 registration edge 84 Seal lip
[0090] 25 plate 85 ridge
[0091] 27 sidewalls 90 specimen plate lid
[0092] 29 sample area 91 alignment tabs
[0093] 31 exterior well 92 Seal
[0094] 32 interior well 93 groove
[0095] 33 plate lip 94 corner
[0096] 35 barcode 95 inner tab surface
[0097] 36 bar code 96 45 degree angle
[0098] 37 Seal 97 chamfer
[0099] 39 chamfer 98 plate sidewall
[0100] 41 corner 99 distance
[0101] 43 groove 101 volume
[0102] 45 volume 105 robotic system
[0103] 47 chamfer 106 workstation
[0104] 49 ridge 107 robot
[0105] 51 recess 108 robotic arm
[0106] 53 lip 109 gripper
[0107] 54 loaded bearing surface 110 holding area
[0108] 55 sidewalls 111 plate
[0109] 60 assay plate lid 112 lid
[0110] 62 cover 113 tabs
[0111] 64 alignment tabs 114 gripper lip
[0112] 65 chamfer 115 registration lip
[0113] 67 holes 120-177 flowchart blocks
[0114] 71 Seal
* * * * *