U.S. patent application number 10/113140 was filed with the patent office on 2002-08-08 for multiwell filter and/or plate.
Invention is credited to Cote, Richard Alexander, Mathus, Gregory, Michaelsen, Alfred L..
Application Number | 20020104795 10/113140 |
Document ID | / |
Family ID | 25355122 |
Filed Date | 2002-08-08 |
United States Patent
Application |
20020104795 |
Kind Code |
A1 |
Cote, Richard Alexander ; et
al. |
August 8, 2002 |
Multiwell filter and/or plate
Abstract
A filter plate for use in biological or chemical applications,
and its method of manufacture, are disclosed. The filter plate
comprises a plurality of structurally interconnected wells which
comprise a matrix of wells having a uniform diameter, each well
having a side wall which defines a vertically extending, generally
cylindrical cavity; a bottom wall which closes the cavity, the
bottom wall having a drainage opening formed therein; a filter
sheet extending across and resting on top of the bottom wall; the
filter sheet being irremovably fixed in position as a result of
engagement with the side wall; a conical nozzle having an external
surface and an internal passage communicating with the drainage
opening in the bottom wall; and a membrane supporting surface
across the internal passage extending from the walls of the
internal passage to a plane normal to the bottom wall.
Inventors: |
Cote, Richard Alexander;
(Boston, MA) ; Mathus, Gregory; (Concord, MA)
; Michaelsen, Alfred L.; (Painted Post, NY) |
Correspondence
Address: |
CORNING INCORPORATED
SP-TI-3-1
CORNING
NY
14831
|
Family ID: |
25355122 |
Appl. No.: |
10/113140 |
Filed: |
March 28, 2002 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10113140 |
Mar 28, 2002 |
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08870313 |
Jun 6, 1997 |
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6391241 |
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Current U.S.
Class: |
210/323.2 ;
210/455; 210/482; 264/153; 422/400 |
Current CPC
Class: |
B01L 3/5025 20130101;
B01L 3/50255 20130101; Y10S 264/48 20130101 |
Class at
Publication: |
210/323.2 ;
264/153; 210/455; 210/482; 422/101 |
International
Class: |
B29C 067/00; B01D
035/02 |
Claims
What is claimed is:
1. A filtration apparatus comprising: a well plate having a
plurality of wells, each well extending through said plate, each
well having open ends; an insert having a plurality of
counterbores, each counterbore defined by a side wall and a bottom
wall, an opening through said bottom wall, each counterbore aligned
with a corresponding and respective well from said well plate, said
side wall of each counterbore surrounding and bonded to one end of
a corresponding well; a filter disc positioned on said bottom wall
of each counterbore and below each said well such that said well
compresses the periphery of said filter disc against said bottom
wall of said counterbore thereby securing said filter disc in
place; a conical nozzle having an external surface and an internal
passage communicating with said opening, said nozzle extending
downwardly from said surface of said counterbore from a point
radially inward from said well; and a supporting surface extending
across said internal passage.
2. The filtration apparatus of claim 1 wherein said internal
passage is funnel shaped.
3. The filtration apparatus of claim 1 wherein said outer surface
of said nozzle intersects said internal passage of said nozzle
forming an edge.
4. The filtration apparatus of claim 1 further comprising an
annular skirt extending from an under surface of said bottom wall
of said counterbore and circumscribing said nozzle.
5. The filtration apparatus of claim 1 having 96 said
interconnected wells.
6. A filtration apparatus comprising a plurality of structurally
interconnected wells which comprise a matrix of wells having a
uniform diameter, each well comprising: a) a side wall which
defines a vertically extending, generally cylindrical cavity; b) a
bottom wall which closes said cavity, said bottom wall having a
drainage opening formed therein; c) a filter sheet extending across
and resting on top of said bottom wall, said filter sheet being
irremovably fixed in position as a result of engagement with said
side wall; d) a conical nozzle having an external surface and an
internal passage communicating with said drainage opening in said
bottom wall, said nozzle extending downwardly from said bottom wall
from a point radially inward from said side wall; and e) a
supporting surface across said internal passage extending from the
walls of said internal passage to a plane normal to said bottom
wall.
7. The filtration apparatus of claim 6 wherein said internal
passage is funnel shaped.
8. The filtration apparatus of claim 6 wherein said external
surface intersects said internal passage forming an edge.
9. The filtration apparatus of claim 6 further comprising an
annular skirt extending from an under surface of said bottom wall
and circumscribing said nozzle.
10. The filtration apparatus of claim 6 having 96 said
interconnected wells.
11. The filtration apparatus of claim 6 having 384 said
interconnected wells.
12. A method of making a filter plate comprising the steps of : a)
molding an insert having a matrix of counterbores, each counterbore
having a bottom wall, an outer rim of predetermined diameter, and
an opening therethrough; b) punching individual filter discs from a
filter sheet and pushing said filter discs into a corresponding
counterbore such that said filter disc substantially covers the
entire bottom wall of the counterbore; c) molding a well plate
against saia insert, said well plate having a top and bottom wall
having a matrix of wells of predetermined diameter extending
through said plate, each said well having open ends at each of said
top corresponds with said matrix of wells such that each said well
aligns with a corresponding counterbore, whereby said well fits
inside the rim of said counterbore thereby forming a lap joint
between each said counterbore and said well, and whereby said well
compresses said filter against said bottom wall of said counterbore
thereby securing said filter disc in place.
13. A method of making a filter plate comprising the steps of: a)
providing an insert having a matrix of counterbores, each
counterbore having a bottom wall and being open at the top, b)
positioning a filter disc in each of said counterbores such that
said filter disc rests upon the top surface of said bottom wall,
and c) insert molding a well plate to said insert thereby forming a
vertically extending well aligned with each of said counterbores,
the side walls of each said well being formed so as to engage each
said filter disc.
14. A method of making a filter plate assembly comprising the steps
of: a) providing a molded insert plate of counterbores, said
counterbores having a predetermined diameter; b) placing on said
insert plate, a die having a matrix of bores, said bores having a
diameter substantially identical to said diameter of said
counterbores and arranged such that each bore positionally aligns
with a corresponding counterbore; c) covering said die with a sheet
of filter material; d) positioning above said filter material, a
matrix of punch units, each unit positionally aligned with a
corresponding bore from said die, each unit comprising a plunger
slidably mounted within a cylindrical punch, each punch having a
radial cutting bottom edge extending beyond said plunger, each said
unit having an outer diameter substantially identical to said
diameter of said corresponding bore such that each unit is capable
of fitting securely into said corresponding bore e) depressing said
matrix of punch units through said filter material thereby cutting
a filter disc from said filter material at each said cutting edge
and such that a bottom surface of said plunger contacts said filter
disc, said matrix of punch units extending into each said bore such
that each said punch unit is at least partially contained within a
corresponding bore; f) extending each said plunger and attached
filter disc into contact with each bottom wall of said counterbore
of said insert while each said punch remains contained within said
bore; g) depositing each said filter disc on a bottom wall of each
respective counterbore; h) removing each said punch unit from each
said counterbore and bore; and i) fitting a well plate having
matrix of open ended wells corresponding in size and location to
said counterbores, against said insert such that each well fits
securely within each corresponding counterbore.
15. A method of making a multiwell plate comprising the steps of:
a) providing a molded insert plate of rings, said rings each having
a substantially flat portion and an annular rim; b) placing on said
insert plate, a die having a matrix of bores, said bores having a
diameter substantially identical to said diameter of said rings and
arranged such that each bore positionally aligns with a
corresponding ring; c) covering said die with a sheet of material;
d) positioning above said material, a matrix of punch units, each
unit positionally aligned with a corresponding bore from said die,
each unit comprising a plunger slidably mounted within a
cylindrical punch, each punch having a radial cutting bottom edge
extending beyond said plunger, each said unit having an outer
diameter substantially identical to said diameter of said
corresponding bore such that each unit is capable of fitting
securely into said corresponding bore e) depressing said matrix of
punch units through said material thereby cutting a disc from said
material at each said cutting edge and such that a bottom surface
of said plunger contacts said disc, said matrix of punch units
extending into each said bore such that each said punch unit is at
least partially contained within a corresponding bore; f) extending
each said plunger and attached disc into contact with each flat
portion of said ring of said insert while each said punch remains
contained within said bore; g) depositing each said disc on said
flat portion of each respective ring; h) removing each said punch
unit from each said counterbore and bore; and i) molding a well
plate having matrix of open ended wells corresponding in size and
location to said rings, against said insert such that each well
fits securely within each corresponding ring.
16. A method of making a multiwell plate comprising the steps of:
a) providing an insert having a matrix of rings, each ring having
an annular support surface around an opening, b) positioning a disc
of material against each said ring such that said disc of material
rests upon said support surface, c) insert molding a well plate to
said insert thereby forming a vertically extending well aligned
with each of said rings, the side walls of each said well being
formed so as to engage each said disc.
17. A method of making a multiwell plate comprising the steps of:
a) molding an insert having a matrix of rings, each ring having a
substantially flat support surface and an outer rim of
predetermined diameter; b) punching individual discs from a sheet
and pushing said discs into contact with said support surface of a
corresponding ring such that said disc substantially covers the
entire opening of said ring; and c) molding a well plate against
said insert, said well plate having a top and bottom wall having a
matrix of wells of predetermined diameter extending through said
plate, each well having open ends at each of said top and bottom
wall, said matrix of rings corresponding with said matrix of wells
such that each said well aligns with a corresponding ring whereby
said well fits inside the rim of said ring thereby forming a lap
joint between each said ring and said well, and whereby said well
compresses said disk against said support surface of said ring
thereby securing said disc in place.
18. A multiwell plate comprising: a well plate having a plurality
of wells, each well extending through said plate, each well having
open ends; an insert having a plurality of rings, each ring having
a substantially flat support surface and an outer rim of
predetermined diameter, each ring aligned with a corresponding and
respective well from said well plate, said outer rim of each ring
surrounding and bonded to one end of a corresponding well; and a
disc of material positioned on said support surface of each ring
and below each said well such said well compresses the periphery of
said disc against said support surface of said ring thereby
securing said disc in place.
Description
BACKGROUND OF THE INVENTION
[0001] The invention relates to a disposable multiwell filter
apparatus for use in biological and biochemical assays that can be
used and is compatible with existing equipment.
[0002] In pharmaceutical and biological research laboratories,
plates with a multitude of wells have replaced traditional test
tubes for assay and analysis. For many years, multi-well laboratory
plates have been manufactured in configurations ranging from 1 well
to 384 wells, and beyond. The wells of multi-well plates are
typically used as reaction vessels in which various assays are
performed. The types of analytical and diagnostic assays are
numerous. The typical areas of use include cell culture, drug
discovery research, immunology, and molecular biology, among
others. Current industry standard multi-well plates are laid out
with 96 wells in an 8.times.12 matrix (mutually perpendicular 8 and
12 well rows). In addition, the height, length and width of the
96-well plates are standardized. This standardization has resulted
in the development of a large array of auxiliary equipment
specifically developed for 96-well formats.
[0003] Many assays or tests require a mixture of particulate or
cellular matter in a fluid medium. The mixture is then subjected to
combination with reagents, separation steps and washing steps. The
end product of such analysis is often a residue of solid matter
which may be extracted for further analysis.
[0004] Separation of solids from fluid medium is often accomplished
by filtration. The separation is accomplished in or on the filter
material by passing the liquid through it. The liquid can be
propelled through the membrane either by a pressure differential or
by centrifugal force. Filter plates that conform to a 96 well
standardized format are known as disclosed in U.S. Pat. Nos.
4,427,415 and 5,047,215. One significant problem that has been
encountered with filter plates adapted for use with a 96 well plate
is that cross contamination may occur between wells. When a unitary
filter sheet is sandwiched between two pieces of plastic molded in
a 96 well format, liquid from one well, upon wetting the filter
material, may wick through the paper to neighboring wells thereby
contaminating the sample contained within that well. One solution
to this problem is offered in U.S. Pat. Nos. 4,948,442 and
5,047,215. In these patents, a 96 well filter plate is disclosed
comprising a filter sheet placed between two plastic plates. One of
the plates has a series of ridges that cut the filter sheet when
the plates are ultrasonically welded together. By cutting the
filter sheet around each well, the possibility of wicking between
neighboring wells is effectively eliminated. A problem with this
design is that it limits the product offering to membranes that can
be cut by the process and to plate materials that can be
ultrasonically welded. In fact, the potential for wicking and cross
contamination still exists when the filter material is not
completely severed in the welding process.
[0005] U.S. Pat. No. 4,427,415 discloses a filter plate of one
piece construction having wells with drain holes in the bottom and
capable of receiving filter discs into the wells. Wicking is
obviously not a problem in this plate because individual filter
discs are used as opposed to a unitary sheet of filter paper. The
filter discs used in this plate are put into each well individually
and are not secured to the bottom of the well. A danger exists with
a filter disc that has not been secured down in that some liquid
from the well could pass under the filter and thereby escape
filtration, resulting in contamination of the filtrate.
[0006] Our invention solves several problems of prior art filter
plate designs by providing a multiwell filter plate in which 1)
filters are securely fastened to the plate without the use of glue
or other potentially contaminant chemical adhesives 2) an expansive
variety of filter materials may be used, 3) a large number of
thermoplastic components may be employed in its construction, and
4) no cross contamination through liquid wicking occurs between
neighboring wells. The preferred embodiment of the present
invention also offers a conical nozzle designed to cause exiting
fluid to create droplets rather than lateral flow along the bottom
of the plate. Further, a ring or skirt will preferably circumscribe
the underside of each filter well. The skirt fits into a
corresponding well of a receiver plate and is designed to prevent
cross contamination that may otherwise occur by splashing of
filtrate.
SUMMARY OF THE INVENTION
[0007] It is therefore an object of the present invention to
provide a disposable filtration device for chemical and biological
tests in which a large number of samples may be tested
simultaneously. Further objects of the present invention are: to
provide a filter plate that will be compatible with existing 96
well cluster plate formats as standardized by the industry; to
provide a filter plate that can be handled by automated robotic
assay equipment; to provide a filter plate having individual wells
having a support grid on the bottom to help support the filter
element, prevent tearing, and allow for an even distribution of
filtered material on the filter; to provide a filter plate in which
liquid from one well can not mix with liquid from a neighboring
well (the filter plate of the present design prevents lateral flow
or cross-talk of liquid through the membrane to other wells); to
prevent cross contamination of filtrate after passing through the
filter and passing to a receiver plate; to provide a filter plate
of two part construction in which each individual well filter is
securely pinned between opposing plates that are insert molded
against each other; and to provide a unique method for the
manufacture of filter plates.
[0008] Briefly, the present invention relates to an improved filter
plate and its method of manufacture. The filter plate is a two part
construction. It comprises a well plate preferably with 96 wells,
each well being open on both ends, molded against a harvester plate
insert preferably having 96 counter-bores, each containing a filter
disc, whereby each counter-bore aligns with a corresponding and
respective well from the well plate, and whereby the diameter of
the counter-bore is greater than the diameter of the well, such
that the well bonds with the outer rim of the counterbore thereby
creating a lap joint. The lap joint also serves the purpose of
fixing the filter disc securely to the insert without the need for
glue or chemical adhesives. During the injection molding process,
extremely high pressures in the mold ensure that the edges of the
filter disc are pressed against the insert.
[0009] The assembled filter plate product has a plurality of
interconnected wells of uniform diameter, each well being defined
by a circular side wall, each of the side walls being
interconnected to the side wall of at least two adjacent wells,
each of the wells being open at one end. Further, the plate has a
bottom wall at the bottom of each of the wells, which is connected
to the side wall, each of the bottom walls having an opening
therein. A conical drainage nozzle having an external surface and
an internal passage communicating with the opening in the bottom
wall, extends downwardly from the bottom wall from a point radially
inward from the side wall. Finally, a filter disc is positioned on
top of the bottom walls of the wells, the peripheries of each
filter being sandwiched between a bottom portion of the side wall
of each well and a top portion of the bottom wall of each well. The
bottom walls have an opening therein, the opening preferably taking
the form of a funnel shaped nozzle. A support grid preferably
extends across the opening in order to provide support for the
filter disc.
[0010] The method of manufacturing the plate comprises several
steps, namely: forming an insert having a plurality of
counter-bores; punching filter discs into the bottom surface of the
counter-bore; and insert molding a well plate against the insert
and filters such that wells from the well plate align with
corresponding counter-bores from the insert thereby forming a lap
joint that effectively secures the filter disc in place. The method
can be extended for use in the manufacture of multiwell plates
which do not have a filter, but require a well bottom of a
different material than the side walls.
DESCRIPTION OF THE FIGURES
[0011] FIG. 1 is a plan view of the insert of the present
invention.
[0012] FIG. 2 is a side view of the insert of the present
invention.
[0013] FIG. 3 is a fragmentary cross sectional view of the insert
of FIG. 1, taken along the section line 3-3 in FIG. 1.
[0014] FIG. 4 is a three dimensional view of the insert of the
present invention.
[0015] FIG. 5 is an enlarged view of the corner of the insert of
FIG. 4.
[0016] FIGS. 6A-6C are cross sectional views of a three step
process for punching filter discs from a unitary sheet of filter
paper, and inserting the discs into the insert.
[0017] FIGS. 7A-7D are cross sectional three dimensional views of
the molding process of the current invention whereby a well plate
is molded against an insert.
[0018] FIGS. 8A-8D are cross sectional two dimensional views of the
molding process shown in FIG. 7.
[0019] FIG. 9 is a multiwell filter plate of the present invention
having a corner section extracted.
[0020] FIG. 10 is an enlargement of the corner of the multiwell
filter plate of FIG. 9 showing a cross section of two adjacent
wells.
[0021] FIG. 11 is a multiwell plate of the present invention having
a corner section extracted.
[0022] FIG. 12 is an enlargement of the corner of the multiwell
plate of FIG. 9 showing a cross section of two adjacent wells.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0023] Shown in FIG. 1 is an insert 10 of the present invention.
The term insert is defined as a harvester plate capable of holding
filter elements. The insert 10 is molded of a preferably
hydrophobic thermoplastic material and preferably has 96 separate
and distinct counter-bores 12 within it. Ideally, the spacings from
the center point of each counter-bore 12 will conform to spacings
between the centers of wells of the industry standardized 96 well
cluster plate. Each counter-bore 12 has an annular lip or rim 14
around its outer periphery. The individual counter-bores 12 are
joined together by adjoining the peripheries of adjacent
counter-bores. Within the periphery of the rim 14, each
counter-bore has a substantially flat bottom wall 16 capable of
seating a filter disc and a depressed center area that forms the
conical drain funnel 25. Further, each counter-bore preferably has
a support grid 18 partially covering the drain hole, provided to
prevent filter material that is seated on the flat bottom wall 16
of a counterbore from tearing during filtration while maximizing
the open filter area for fluid flow.
[0024] FIG. 2 shows a side view of the insert of the present
invention. Each counter-bore has a funnel shaped drain hole
therethrough. Preferably, below the flat surface area of the
counterbore, is an annular skirt 20. The annular skirt serves two
functions. First, the annular skirt 20 serves as a guidance system
when aligning the filter plate with a 96 well receiving plate. The
skirt 20 fits into a corresponding well in the 96 well plate into
which filtrate is to be transferred. Any lateral movement of the
filter plate, once engaged with the receiving plate, is repressed
by the plurality of skirts sitting in the respective wells of the
receiver plate. Second, the skirt 20 serves to minimize any
contamination between wells of a receiver plate by guarding against
aerosols or splashing of liquid filtrate as it transfers into the
receiver plate.
[0025] FIG. 3 shows a cross sectional view of one counter-bore 12
from an insert of the present invention. The counter-bore has a
substantially flat bottom wall-16 to support a filter disc, an
annular rim 14 around the periphery, a grid support 18, an annular
skirt 20 and a conical nozzle serving as a drain hole 22 and
extending downwardly from the bottom wall 16, preferably
terminating at a point above the termination point of the skirt.
The nozzle has an external surface 24, and an internal passage 25
that communicates with the bottom wall 16 of the counterbore 12.
The internal passage 25 is preferably funnel shaped. The opening or
drain hole 22 in the nozzle, where the internal passage 25 and
external surface 24 of the nozzle meet, will preferably be quite
small relative to the diameter of the bottom surface of the
counter-bore. The small diameter and material surface energy are
intended to keep the contents of a filter well from flowing until a
significant driving force is applied. The conical external surface
24 of the nozzle is designed so that its surface intersects the
internal passage 25 to form a sharp edge. The purpose of the sharp
edge is to cause the draining fluid to form a droplet, rather than
to allow flow laterally to any adjacent well thereby causing fluid
cross-contamination of the filtrate along the under surface of the
insert portion of the filter plate. Additionally, the edge will
cause smaller droplets to form at the opening than would otherwise
form without an edge. Ideally, a chamfered edge will be provided on
the bottom of the skirt (not shown). The purpose of this chamfer is
to guide the filter plate into the correct location over the
receiver plate. This design is intended to make the plate easy to
handle by a robotic placement system.
[0026] FIGS. 4 and 5 show the insert 10 from above and in a
three-dimensional view. The insert 10 contains a matrix of
counter-bores 12 based upon the standard 96-well standard plate.
Each counterbore 12 has an annular rim 14 around its periphery. A
grid system 18 provides support over each drain hole. The grid
system is comprised of a series of molded supports 15 that extend
across the opening in the bottom wall 16 of the counterbore 12. The
supports 15 extend across the internal passage 25 of the nozzle,
are attached to the walls of the internal passage and project
upward to a plane normal the top surface of the bottom wall of the
counterbore. The grid system creates a substantially flat surface
entirely across the bottom wall of the counterbore. The bottom wall
is therefore able to provide support for a filter disc, and prevent
any tearing of the disc, while still allowing filtrate to be drawn
into the funnel shaped passage. The grid system further allows
liquid to be drawn through the filter disc from a greater surface
area than the prior art devices. This creates a more uniform
distribution of filtered material on the disc and allows for a
smoother flow of liquid through the plate.
[0027] FIGS. 6A-6C show the process of punching and inserting a
filter disc into a counterbore of the insert. A molded insert 10 is
placed within a punch machine preferably having 96 punches 26 sized
to cut membranes that will fit into the corresponding 96
counter-bores 12 of the insert. A filter sheet 28 of the desired
material is placed between the insert 10 and the punch mechanism
26. A series of aligned bores 30 from the die side of the punch
will be placed between the filter sheet 28 and each counter-bore 12
of the insert. The insertion of the filter discs preferably takes
place in a two step process, first a punch, then an insertion.
[0028] For clarity, FIG. 6A shows only a single counter-bore 12. A
bore 30 preferably made of hardened steel is located between the
counter-bore 12 and a filter sheet 28. Positioned above the filter
sheet 28 is a cylindrical plunger 32. The plunger 32 has a bottom
wall and is surrounded by a cylindrical punch 26. The plunger 32 is
slideably mounted within the punch 26. The punch 26 terminates at
its base in a radial cutting edge 34. The punch and plunger
together make up a punch unit and are surrounded by a sleeve 36.
The outer diameter of the punch 26 is approximately the same as the
inner diameter of the bore 30 such that the punch fits snugly into
the bore. The diameter of the bore 30 is approximately identical to
the diameter of the counter-bore 12. FIG. 6B shows the plunger 32
having been thrust downward into the bore 30. The cutting edge 34
of the punch has severed the filter sheet 28 such that a filter
disc 38 has been cut and pushed into the bore 30. In FIG. 6C, the
punch 26 has stopped extending into the bore 30, while the plunger
32 has continued pushing the filter disc 38 down into the
counter-bore 12 and against its bottom wall 16. The plunger 32 and
the punch 26 are then retracted, leaving an insert 10 having a
filter disk 38 positioned along the bottom wall 16 of the
counterbore 12. Of course, it will be appreciated that as
indicated, the described sequence will be performed simultaneously
on a multiplicity of wells, e.g. 96 wells. The counterbore 12 as
shown in FIGS. 6A-6C is only one from a matrix of counterbores
making up an insert 10. Further, bore 30 is only one bore from a
die having a matrix of bores that positionally align with the
insert. Likewise, the punch unit comprising a plunger 32 surrounded
by a cylindrical punch 26, is one of a matrix of punch units that
positionally align with individual bores of the bore plate and
individual counterbores of the insert. Preferably, sleeve 36, which
is one sleeve from a precision carrier or guide plate, will
encapsulate each punch unit as a protective measure.
[0029] FIGS. 7A-7D and FIGS. 8A-8D show the insert molding
technique that may be employed to obtain the filter plate of the
present invention. FIGS. 7A-7D show the molding technique of one
filter well, a portion of a plate of preferably 96 interconnected
filter wells, in three-dimensional view. FIGS. 8A-8D show the same
steps in cross sectional views. The mold which will accept this
insert will have a cavity geometry that will form a standard 96
well plate against the insert, with the insert forming the bottom
of the plate. The mold of FIG. 7A has two parts, an upper mold 40
and a lower mold 42. The lower mold 42 is designed to form a nest
44 for the pre-molded insert 10, as well as create external molded
surfaces of the finished part. The upper mold 40 has a set of 96
core pins 46 that serve both to form the inside surfaces of the
wells and to protect and hold each filter disc 38 in place while
the material flows into the mold. The diameter of the core pins 46
are preferably smaller than the diameter of the filter discs 38 so
that, when the mold closes, the outer edges of the filter discs
will be exposed to the mold cavity and thus wiLl also be exposed to
material flowing into the mold. FIGS. 7B and 8B show the mold
closed with the upper part 40 and lower part 42 of the mold pressed
together. The core pin 46 is pressing the filter disc 38 in place.
Material flows into the mold through a gate and flows across the
cavity, thereby forming the well plate 48. The gate is located in
such a position as to optimize mold flow. The formed well plate is
a plate preferably having 96 wells that extend through the plate,
each well having open ends on each of its top and bottom surfaces.
FIGS. 7C and 8C show the mold after the thermoplastic material has
filled the mold and formed the well plate 48. FIGS. 7D and 8D show
the finished ware after it has been removed from the mold. The
flange 56 would, of course, connect to corresponding flanges on
adjacent wells. The well plate 48 contacts the filter disc 38
around the entire periphery of each well wall 50. The outer rim 14
of each counter-bore 12 and the lower wall 50 of each well actually
bond together during the molding process and form lap joints 52
along their entire periphery. Anywhere the new material contacts
the insert directly, the materials will be bonded. The well plate
48 and insert 10 are effectively bonded at each well along the lap
joints 52. The well plate 48 is molded against the outer periphery
of the filter disc 38 so as to position it securely against the
bottom wall 16 of the insert 10. In some cases, depending on the
membrane material, the filter disc 38 will bond to the material
forming the well wall 50 thereby further securing the membrane in
place.
[0030] The insert molding technique as described lends a further
advantage over press fitting techniques or techniques that require
ultrasonically welding two plates together. Thermoplastic materials
have a tendency to change shape slightly upon cooling. Alignment
between two separately molded parts can be compromised by this
cooling process resulting, at times, in an improper fit between
parts. However, in the present invention, since the well plate is
molded against the insert, a reproducible dependable fit is
guaranteed. Thereby, the fit between plates as described is
inherently superior to a fit obtained by matching together two
separately molded pieces.
[0031] Referring to FIG. 9 and 10, the resultant filter plate 60
has a plurality of wells 62 arranged in an 8.times.12 matrix. Each
individual well is separated from the other, each containing a
separate filter disc 38. No wicking or cross contamination between
wells 62 in the filter plate 60 is possible because filter discs 38
are cut from the filter sheet before molding, not as part of the
molding process. Each individual well is sealed from neighboring
wells and no liquid transfer is possible through the overlapping
and material bonded joint 52 formed between the well plate 48 and
the insert 10.
[0032] It should be noted that the process for manufacturing filter
plates can also be employed in the manufacture of 1.times.N well
filter strips or individual filters. Further, filter plates can
have wells of any number, for example 384 wells arranged in a
16.times.24 matrix.
[0033] It should also be noted that the process for manufacturing
filter plates is not limited to wells that have a circular cross
section. The counterbores of the insert and wells of the well plate
may be oval, square, rectangular, etc. The discs that are punched
from the sheet of material will, of course correspond to the shape
of the well and therefore likewise may be oval, square,
rectangular, etc. as punched from an accordingly shaped punch
unit.
[0034] The process for manufacturing filter plates can also be
employed for producing other plates that require a well bottom of a
different material than the side walls. For example, for the
production of a multiwell plate having wells having opaque side
walls and transparent bottoms, a transparent sheet or film such as
a fluoropolymer film, may be substituted for the filter membrane
material herein before described. In this embodiment and referring
to FIGS. 11 and 12, the insert 60 consists of a molded support
having a matrix of rings 62 corresponding to the desired multiwell
plate 61. The rings 62, instead of having funnel shaped nozzles
extending downwardly from the insert as described in the filter
plate manufacturing process, are open throughout the center 64.
Each ring 62 preferably has a flat support portion 66 in a plane
parallel to the plane of the insert 60, and a substantially
perpendicular annular rim 68 circumscribing the outer periphery of
the flat support portion 66. The film is then punched by the method
previously discussed, and individual discs of the film material are
placed against the flat support portion of the ring of the insert.
The punch mechanism is preferably sized such that a punched disk of
transparent film will be supported by the flat portion and will fit
against the annular rim. A well plate is then molded against the
insert as previously described. The material of each annular rim
bonds with the material of the well plate and each disc of
transparent film is pinned between the flat support portion of each
ring and the wall of each well. The resultant plate has wells 74
with bottoms 70 consisting of the transparent film material and
sidewalls 72 of a different material, for example, opaque
polystyrene. Punching individual discs from the transparent sheet
also serves the purpose of preventing optical crosstalk between
wells that might otherwise occur through a unitary sheet. The rings
62 of the insert may also be opaque and extend below the surface of
the well bottom 70, thereby further preventing optical crosstalk
between the wells 74.
[0035] Although preferred embodiments of the invention have been
disclosed, other embodiments may be perceived without departing
from the scope of the invention, as defined by the appended
claims.
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