U.S. patent application number 12/577003 was filed with the patent office on 2010-04-15 for pipette tip handling devices and methods.
Invention is credited to Arta Motadel.
Application Number | 20100089938 12/577003 |
Document ID | / |
Family ID | 42097967 |
Filed Date | 2010-04-15 |
United States Patent
Application |
20100089938 |
Kind Code |
A1 |
Motadel; Arta |
April 15, 2010 |
PIPETTE TIP HANDLING DEVICES AND METHODS
Abstract
Discussed herein are methods and devices for storing, handling,
loading or dispensing of pipette tips. Some embodiments allow
repetitive loading of an array of multiple pipette tips that are
stored in a nested configuration.
Inventors: |
Motadel; Arta; (San Diego,
CA) |
Correspondence
Address: |
GRANT ANDERSON LLP;C/O PORTFOLIOIP
P.O. BOX 52050
MINNEAPOLIS
MN
55402
US
|
Family ID: |
42097967 |
Appl. No.: |
12/577003 |
Filed: |
October 9, 2009 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
12422250 |
Apr 11, 2009 |
|
|
|
12577003 |
|
|
|
|
61044243 |
Apr 11, 2008 |
|
|
|
Current U.S.
Class: |
221/1 ; 221/208;
221/282 |
Current CPC
Class: |
B01L 2200/025 20130101;
B01L 9/543 20130101; G01N 2035/103 20130101; G01N 2035/0427
20130101; B01L 2200/14 20130101; B01L 2300/0809 20130101 |
Class at
Publication: |
221/1 ; 221/282;
221/208 |
International
Class: |
B65D 83/02 20060101
B65D083/02 |
Claims
1. A pipette tip dispensing device, comprising a housing and an
actuator plate within the housing, wherein the actuator plate
includes a plurality of abutments having a star-shaped cross
section.
2. The pipette tip dispensing device of claim 1, wherein each
abutment comprises a six-member star-shaped cross section.
3. An actuator plate for use in a pipette tip dispensing device
comprising a plurality of abutments having a star-shaped cross
section.
4. The actuator plate of claim 3, wherein each abutment comprises a
six-member star-shaped cross section.
5. A method comprising (a) providing a pipette tip dispensing
device that includes a housing, an actuator plate within the
housing, wherein the actuator plate includes a plurality of
abutments having a star-shaped cross section, and arrays of nested
pipette tips engaged with the abutments; and (b) applying a
downward force on the housing, thereby dispensing an array of
pipette tips from the dispensing device.
6. The method of claim 5, wherein each abutment comprises a
six-member star-shaped cross section.
Description
RELATED PATENT APPLICATIONS
[0001] This patent application is a continuation-in-part of U.S.
patent application Ser. No. 12/422,250 filed on Apr. 11, 2009,
which claims the benefit of U.S. Provisional Patent Application No.
61/044,243 filed on Apr. 11, 2008. Each of these patent
applications is entitled PIPETTE TIP HANDLING DEVICES AND METHODS
and names Arta Motadel as an inventor, and the foregoing patent
applications are designated by attorney docket nos. PEL-1001-UT and
PEL-1001-PV, respectively. The entire content of the foregoing
patent applications hereby is incorporated by reference, including
all text, tables and drawings.
FIELD
[0002] Described herein are method and device embodiments for
storing, loading or handling of pipette tips. Some embodiments
allow for convenient loading of multiple batches of pipette tips
into loading blocks or plates with a minimal amount of waste.
BACKGROUND
[0003] Pipette tips are used in large quantities for a wide variety
of applications related to liquid material handling, such as
measuring, dispensing and aspirating of the liquids. Pipette tips
are often used in conjunction with hand held pipettors, such as
mechanical or electrical pipettors, that have distal nozzles that
are configured to be releasably engaged with a proximal port or
opening of a pipette tip in a sealed relationship. The pipettor may
then be used to apply a vacuum or otherwise decrease the pressure
in the interior volume of the pipette tip in order to aspirate
liquid into the pipette tip for transfer to another location. For
some applications a single pipettor may be used, however, for some
applications, particularly automated or robotic applications,
pipettors or manifolds having multiple distal nozzles may be used
to engage multiple pipettor tips disposed in a loading plate or
block simultaneously.
[0004] For such configurations, after the pipette tips are seated
onto the nozzles and removed from the loading block, a new set of
pipette tips must be provided for the next cycle of liquid
handling. Typically, a new set of pipette tips are taken from a
package in a storage plate and loading block in a regularly spaced
array and positioned for seating with the distal nozzles of the
manifold. Because of the difficulty of manually handling large
numbers of pipette tips due to the time consuming nature of such
handling as well as the risk of contamination, pipette tips are
generally pre-packaged in regularly spaced arrays spaced in
pre-determined spacing to match the spacing of the array of distal
nozzles. The pipette tips may be transferred from the packaging in
a loading plate that is part of the packaging but may also include
an entire loading plate and loading block in order to maintain the
array configuration during handling and transfer to a location for
seating to the manifold or pipettor.
[0005] For such multiple pipette tip arrays, because each pipette
tip may require a significant amount of axial force between the
respective nozzle and proximal opening of the pipette tip in order
to be properly seated, the cumulative force required to seat an
array of pipette tips may be quite high. For example, a 96 tip
manifold may exert about 75 pounds to about 250 pounds of force on
a loading block having a 96 tip array. Because of the amount of
force generated, the loading block that supports the loading plate
must be structurally strong and able to withstand the cumulative
axial force without significant deformation. To be this strong, the
block requires a significant amount of mass of material which is
typically a polymer. Once the distal nozzles of the manifold have
engaged and seated the pipette tips and withdrawn them from the
loading plate and block, the loading block and plate are disposed
of and replaced with a new loading block and plate that is full of
new pipette tips. As a result, a user performing a high volume of
such liquid handling cycles will be disposing of a large volume of
loading blocks and plates which generates a large volume of polymer
waste which may be environmentally unsound in many instances.
[0006] For embodiments of pipette tip arrays that transfer in a
loading plate without the loading block, the loading tray is lifted
or moved from the packaging, as necessary, and positioned over a
loading block. After each seating of an array of pipette tips, the
loading plate must be removed or the z-axis position of the top of
the plate will change with the addition of each new loading plate
from a new package of pipette tips.
SUMMARY
[0007] Some embodiments of a pipette tip dispensing device, include
a displacement actuator having an actuator housing with a top
portion, four sides, and an inner surface. The actuator housing
also has a plurality of regularly spaced detent members disposed on
at least one side of the housing and a plurality of proximal
alignment members disposed in a regularly spaced array on a top
portion of the actuator with each proximal alignment member
configured to releasably engage and restrict lateral displacement
of a proximal end of a pipette tip engaged therewith. An alignment
housing of the device includes an outside surface in contact with
the inside surface of the displacement actuator housing in a
sliding arrangement. A plurality of regularly spaced detent members
are configured to releasably engage the detent members of the
actuator housing. In addition, the detent members of the alignment
housing have a regular spacing that is substantially the same as
the regular spacing of the detent members of the actuator housing.
A proximal opening of the alignment housing has an inside surface
configured to engage outer lateral sides of a loading block. A
distal barrier element is disposed at a top portion of the
alignment housing and includes a plurality of restrictive apertures
which are substantially aligned with corresponding proximal
alignment members.
[0008] Some embodiments of a pipette tip dispensing device include
a displacement actuator having an actuator housing that includes an
inside surface, a clear thin rigid material formed into a
substantially rectangular configuration with an open bottom
portion, substantially planar sides and a plurality of regularly
spaced detent members disposed on at least one sides thereof. A
proximal actuator plate (also referred to herein as an "activator
plate") of the actuator includes a plurality of proximal alignment
members disposed substantially in a plane in a regularly spaced
array and each proximal alignment member configured to releasably
engage and restrict lateral displacement of a proximal end of a
pipette tip engaged therewith. An alignment housing assembly of the
device includes a substantially rectangular structure having an
outside surface configured to engage the inside surface of the
actuator housing, four sides formed from a clear thin substantially
rigid material with a plurality of regularly spaced detent members
configured to releasably engage the detent members of the actuator
housing and having a regular spacing that is substantially the same
as the regular spacing of the detent members of the actuator
housing. A proximal opening of the alignment housing is configured
to engage an outside perimeter of a loading block. An outer surface
of the alignment housing is configured to slidingly engage an inner
surface of the actuator housing so as to allow relative movement
therebetween. A substantially planar distal barrier element is
disposed at a top portion of the alignment housing and has a
plurality of restrictive apertures which are substantially aligned
with respective proximal alignment members and which are configured
to engage an outside surface of a pipette tip, restrict lateral
displacement of a pipette tip and resist axial displacement of the
pipette tip until an axial force threshold imparted to the pipette
tip is reached. Once a threshold axial force is imparted to a
pipette tip engaged by restrictive aperture, the pipette tip will
pass through the restrictive aperture so as to be dispensed.
[0009] Some embodiments of a method of simultaneously dispensing an
array of multiple pipette tips into a loading block, include
providing a dispensing device that includes an array of regularly
spaced pipette tips and engaging the dispensing device with a
loading block such that distal ends of pipette tips which are
engaged with restrictive apertures of a barrier member of the
dispensing device are disposed within receptacles of the loading
block. Thereafter, an actuator of the dispensing device is actuated
so as to apply an axial force on the array of pipette tips engaged
with the restrictive apertures of the dispensing device until a
threshold axial force is applied and the array of pipette tips
engaged with the restrictive apertures is dispensed into respective
receptacles in the loading block.
[0010] In some embodiments, provided herein is a pipette tip
dispensing device, comprising a displacement actuator which
includes an actuator housing having a top portion, four sides, and
an inner surface, a plurality of regularly spaced detent members
disposed on at least one side of the housing, and a plurality of
proximal alignment members disposed in a regularly spaced array on
a top portion of the actuator with each proximal alignment member
configured to releasably engage and restrict lateral displacement
of a proximal end of a pipette tip engaged therewith. The device
also comprises an alignment housing including an outside surface in
contact with the inside surface of the displacement actuator
housing in a sliding arrangement, a plurality of regularly spaced
detent members configured to releasably engage the detent members
of the actuator housing and having a regular spacing that is
substantially the same as the regular spacing of the detent members
of the actuator housing, and a proximal opening having an inside
surface configured to engage outer lateral sides of a loading block
26. The device also comprises a distal barrier element disposed at
a top portion of the alignment housing having a plurality of
restrictive apertures which are substantially aligned with
corresponding proximal alignment members.
[0011] In certain embodiments, the pipette tip dispensing device
further comprises a plurality of pipette tips disposed in a nested,
regularly spaced array between the respective proximal alignment
members and restrictive apertures with a longitudinal axis of each
nested set of pipette tips being substantially aligned and coaxial
with the respective proximal alignment members and restrictive
apertures. The regular spacing of the restrictive apertures and
proximal alignment members can be about 9 mm. The proximal
alignment members comprise cone shaped abutments extending from a
distal surface of the proximal actuator plate.
[0012] In some embodiments, a pipette tip dispensing device has
actuator housing and alignment housing comprised of a polymer
material. The polymer material of the actuator housing and
alignment housing comprises molded polypropylene in some
embodiments. The polymer material of the actuator housing and
alignment housing comprises a thickness of about 0.005 inches to
about 0.05 inches in certain embodiments.
[0013] Provided also is a pipette tip dispensing device having an
actuator housing comprised of a telescoping arrangement which has
multiple housing elements. The restrictive apertures of the barrier
element comprise holes sized to mechanically engage a major outer
transverse dimension of a proximal portion of a pipette tip and
prevent axial displacement of the proximal portion through the
aperture until a threshold axial force is applied to the engaged
pipette tip at which time the proximal portion is deflected and
compressed to allow passage through the restrictive aperture.
[0014] In some embodiments, provided is a pipette tip dispensing
device, comprising a displacement actuator comprising an actuator
housing that includes an inside surface, a clear thin rigid
material formed into a substantially rectangular configuration with
an open bottom portion, substantially planar sides and a plurality
of regularly spaced detent members disposed on at least one sides
thereof, and a proximal actuator plate having a plurality of
proximal alignment members disposed substantially in a plane in a
regularly spaced array and each proximal alignment member
configured to releasably engage and restrict lateral displacement
of a proximal end of a pipette tip engaged therewith; an alignment
housing assembly including a substantially rectangular structure
having an outside surface configured to engage the inside surface
of the actuator housing, four sides formed from a clear thin
substantially rigid material with a plurality of regularly spaced
detent members configured to releasably engage the detent members
of the actuator housing and having a regular spacing that is
substantially the same as the regular spacing of the detent members
of the actuator housing, and a proximal opening configured to
engage an outside perimeter of a loading block, an outer surface
configured to slidingly engage an inner surface of the actuator
housing so as to allow relative movement there between; and a
substantially planar distal barrier element disposed at a top
portion of the alignment housing having a plurality of restrictive
apertures which are substantially aligned with respective proximal
alignment members and which are configured to engage an outside
surface of a pipette tip, restrict lateral displacement of a
pipette tip and resist axial displacement of the pipette tip until
an axial force threshold imparted to the pipette tip is
reached.
[0015] In certain embodiments, the pipette tip dispensing device
further comprises a plurality of pipette tips disposed in a nested,
regularly spaced array between the respective proximal alignment
members and restrictive apertures with a longitudinal axis of each
nested set of pipette tips being substantially aligned and coaxial
with the respective proximal alignment members and restrictive
apertures. In this embodiment, the pipette tip dispensing device
can have restrictive apertures and proximal alignment members
having regular spacing about 9 mm. The pipette tip dispensing
device also can have proximal alignment members comprising cone
shaped abutments extending from a distal surface of the proximal
actuator plate. The pipette tip dispensing device can have an
actuator housing and alignment housing comprising a polymer
material. The polymer material of the actuator housing and
alignment housing can comprise molded polypropylene. The polymer
material of the actuator housing and alignment housing can comprise
a thickness of about 0.005 inches to about 0.05 inches. The
actuator housing can also comprise a telescoping arrangement having
multiple housing elements. The restrictive apertures of the barrier
element can also comprise holes sized to mechanically engage a
major outer transverse dimension of a proximal portion of a pipette
tip and prevent axial displacement of the proximal portion through
the aperture until a threshold axial force is applied to the
engaged pipette tip at which time the proximal portion is deflected
and compressed to allow passage through the restrictive
aperture.
[0016] Also provided is a method of simultaneously dispensing an
array of multiple pipette tips into a loading block, which
comprises providing a dispensing device that includes an array of
regularly spaced pipette tips; engaging the dispensing device with
a loading block such that distal ends of pipette tips which are
engaged with restrictive apertures of a barrier member of the
dispensing device are disposed within receptacles of the loading
block; actuating an actuator of the dispensing device so as to
apply an axial force on the array of pipette tips engaged with the
restrictive apertures of the dispensing device to overcome a
threshold axial force and eject the array of pipette tips engaged
with the restrictive apertures into respective receptacles in the
loading block.
[0017] In some embodiments, the dispensing device further comprises
a plurality of pipette tips disposed in a nested, regularly spaced
array between respective proximal alignment members and restrictive
apertures with a longitudinal axis of each nested set of pipette
tips being substantially aligned and coaxial with the respective
proximal alignment members and restrictive apertures and further
comprising multiple actuations of the actuator in order to eject a
plurality of arrays of multiple pipette tips.
[0018] In certain embodiments, the actuator further comprises a
plurality of regularly spaced proximal alignment members configured
as cone shaped abutments extending from a distal surface of a
proximal actuator plate, the barrier member comprises a barrier
plate and where actuating the actuator comprises moving the
proximal actuator plate towards the barrier plate with threshold
axial force sufficient to force an array of pipette tips through
the restrictive apertures of the barrier plate.
[0019] In some embodiments, the actuator housing and alignment
housing comprise a clear polymer material and further comprising
visualizing the ejection of the array of multiple pipette tips from
the restrictive apertures of the barrier member during actuation.
The actuator housing can comprise a telescoping arrangement having
multiple housing elements and where actuation of the actuator
comprises collapsing the multiple housing elements from an extended
state to a collapsed nested state. The restrictive apertures of the
barrier element can comprise holes sized to mechanically engage a
major outer transverse dimension of a proximal portion of a pipette
tip and prevent axial displacement of the proximal portion through
the aperture until a threshold axial force is applied to the
engaged pipette tip and further comprising actuating the actuator
until the proximal portion of each pipette tip of the array of
multiple pipette tips engaged with the restrictive apertures are
deflected and compressed to allow passage through the restrictive
apertures and barrier member.
[0020] Provided in some embodiments is a pipette tip dispensing
device, comprise (a) a housing; (b) a distal barrier plate in
effective connection with the housing; and (c) a plurality of
nested pipette tip units where each unit is aligned with a channel
in the distal barrier plate, and where the distal barrier plate
comprises (i) a plurality of channels, where each channel has a
diameter larger than the widest portion of a pipette tip; (ii) a
top surface, and (iii) a bottom surface that comprises a plurality
of tails around some or all of the channels, where: (1) the tails
extend in a nearly perpendicular orientation from the bottom
surface, and (2) the tails around each channel contact a pipette
tip when a pipette tip is dispensed and passes by the tails,
thereby imparting (e.g., applying) a frictional force on the
pipette tip when it is dispensed. In some embodiments, the tails
deflect outwards against the pipette tip before, and/or at the same
time the pipette tip is being dispensed (e.g., the pipette tip is
translating), and sometimes the tails contact the proximal portion
of a pipette tip. In some embodiments, a subset of channels in the
distal barrier plate are surrounded by tails that eject pipette
tips of an array at one time, and another subset of channels in the
plate are surrounded by tails that eject pipette tips of the same
array at another time. A distal barrier plate may include 2, 3, 4,
5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 of such
subsets of channels.
[0021] In some embodiments pertaining to a dispensing device
described in the preceding paragraph, the top surface and/or the
bottom surface is substantial flat or planar. In certain
embodiments, each channel in the dispensing device can comprise 2,
3, 4, 5, 6, 7, 8, 9, 10 or more tails. Each channel of the barrier
plate can comprise tails of the same length. In some embodiments,
each channel of the barrier plate can comprise tails of different
lengths in some embodiments. Channels located in the center of the
barrier plate can comprise the longest tails. In certain
embodiments, channels located in the center of the barrier plate
can comprise the shortest tails. Subsequent channels concentrically
disposed about a central longitudinal axis can comprise
sequentially shorter tails in length in a stepwise manner in some
embodiments. In certain embodiments, subsequent channels
concentrically disposed about a central longitudinal axis can
comprise sequentially longer tails in length in a stepwise manner.
Channels located in the center of the barrier plate along the X
axis can comprise tails of the same length and channels along the Y
axis comprise tails of varying length in some embodiments. Channels
located in the center of the barrier plate along the Y axis can
comprise tails of the same length and channels along the X axis
comprise tails of varying length in certain embodiments. Channels
located in the center of the barrier plate along the X and Y axes
can comprise tails of varying length in some embodiments. Each
channel can comprise an even number of tails in certain
embodiments. Tails directly opposite one another around a channel
can have the same length, and in some embodiments, tails directly
opposite one another around a channel can have a different length.
Tails adjacent to one another can have a different length in
certain embodiments. The tails can be at an internal angle of about
89.degree. to about 80.degree. from the bottom surface of the
distal barrier plate in some embodiments. The tails can be at an
internal angle between 88-85.degree., 87-84.degree., 86-83.degree.
or 86-85.degree. from the bottom surface of the distal barrier
plate in some embodiments. The tails can be at an internal angle of
about 87.degree. from the bottom surface of the distal barrier
plate in certain embodiments, and tails sometimes can be between
0.01 .mu.m-2.0 mm in length. The tails can be between 0.05 .mu.m
-2.0 mm in length in certain embodiments. The tails around a
channel are not in the channel in some embodiments. In certain
embodiments, the housing can comprise (a) an actuator housing
comprising a top portion, four sides, an inner surface, and a
plurality of regularly spaced detent members disposed on at least
one side of the housing, and (b) an alignment housing comprising an
outside surface in contact with the inside surface of the actuator
housing in a sliding arrangement, a plurality of regularly spaced
detent members configured to releasably engage the detent members
of the actuator housing and having a regular spacing that is
substantially the same as the regular spacing of the detent members
of the actuator housing, and a proximal opening having an inside
surface configured to engage outer lateral sides of a loading block
in certain embodiments. The housing can comprise a polymer
material, and the polymer material of the housing can comprise
molded polypropylene in some embodiments. The polymer material of
the housing can comprise a thickness of about 0.005 inches to about
0.05 inches. The actuator housing can comprise a telescoping
arrangement having multiple housing elements. The alignment housing
can comprise a flange or a footing for the housing to rest in some
embodiments. The actuator housing can comprise a member on the top
portion of the actuator that maintains contact with and restricts
lateral displacement of the proximal portion of the pipette tips in
certain embodiments, where the member can be selected from the
group consisting of foam, a raised grid, and a plurality of
proximal alignment members in some embodiments. The device can
comprise one or more arrays of 96, 384, 1356 or more pipette tips.
A pipette tip unit can be arranged in an array of pipette tip
units, and each pipette tip unit can comprise 2, 3, 4, 5, 6, 7, 8,
9, 10, 11, 12, 13, 14 or more nested pipette tips in some
embodiments.
[0022] Also provided in some embodiments is a distal barrier plate
that can be part of a pipette tip dispenser and is not in
association with pipette tips, that comprises (a) a plurality of
channels, where each channel comprises a diameter larger than the
widest portion of a pipette tip; (b) a top surface; and (c) a
bottom surface that comprises a plurality of tails around some or
all of the channels, where: (i) the tails extend in a nearly
perpendicular orientation from the bottom surface, and (ii) the
tails around each channel contact a pipette tip when a pipette tip
is dispensed and passes by the tails, thereby applying a frictional
force on the pipette tip when it is dispensed. In some embodiments,
the tails deflect outwards against the pipette tip before the
pipette tip is dispensed, and/or at the same time the pipette tip
is being dispensed (e.g., the pipette tip is translating), and
sometimes the tails contact the proximal portion of a pipette tip.
In some embodiments, a subset of channels in the distal barrier
plate are surrounded by tails that eject pipette tips of an array
at one time, and another subset of channels in the plate are
surrounded by tails that eject pipette tips of the same array at
another time. A distal barrier plate may include 2, 3, 4, 5, 6, 7,
8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 of such subsets
of channels.
[0023] In some embodiments pertaining to a dispensing devices
described in the preceding paragraph, the top surface and/or the
bottom surface is substantial flat or planar. In certain
embodiments, each channel can comprises 2, 3, 4, 5, 6, 7, 8, 9, 10
or more tails. Each channel of the barrier plate can comprise tails
of the same length, and in some embodiments each channel of the
barrier plate can comprise tails of different lengths. Channels
located in the center of the barrier plate can comprise the longest
tails. In certain embodiments, channels located in the center of
the barrier plate can comprise the shortest tails. Subsequent
channels concentrically disposed about a central longitudinal axis
can comprise sequentially shorter tails in length in a stepwise
manner. In certain embodiments, subsequent channels concentrically
disposed about a central longitudinal axis can comprise
sequentially longer tails in length in a stepwise manner. Channels
located in the center of the barrier plate along the X axis can
comprise tails of the same length and channels along the Y axis can
comprise tails of varying length in certain embodiments. In some
embodiments, channels located in the center of the barrier plate
along the Y axis can comprise tails of the same length and channels
along the X axis can comprise tails of varying length. Channels
located in the center of the barrier plate along the X and Y axes
can comprise tails of varying length in some embodiments. Each
channel can comprise an even number of tails. Tails directly
opposite one another around a channel can have the same length in
some embodiments. In certain embodiments, tails directly opposite
one another around a channel can have a different length. Tails
adjacent to one another can have a different length in some
embodiments. In certain embodiments, tails are at an internal angle
of about 89.degree. to about 80.degree. from the bottom surface of
the distal barrier plate. The tails can be at an internal angle
between 88-85.degree., 87-84.degree., 86-83.degree. or
86-85.degree. from the bottom surface of the distal barrier plate
in some embodiments. In certain embodiments, the tails can be at an
internal angle of about 87.degree. from the bottom surface of the
distal barrier plate. The tails can be between 0.01 .mu.m-2.0 mm in
length, and sometimes the tails can be between 0.05 .mu.m-2.0 mm in
length. The tails around a channel are not in the channel in some
embodiments.
[0024] Provided also in some embodiments is a method for
simultaneously dispensing an array of pipette tips into a loading
block, which comprises (a) providing a dispensing device that
includes an array of regularly spaced pipette tips; (b) engaging
the dispensing device with a loading block such that distal ends of
pipette tips are disposed above or within receptacles of the
loading block, the barrier plate comprising (i) a plurality of
channels, where each channel has a diameter larger than the widest
portion of a pipette tip; (ii) a top surface; and (iii) a bottom
surface that comprises a plurality of tails around some or all of
the channels, where the tails extend in a nearly perpendicular
orientation from the bottom surface; and (c) actuating an actuator
of the dispensing device so as to apply an axial force on the array
of pipette tips, where the axial force dispenses the array of
pipette tips through the channels and past the tails, whereby the
tails contact the pipette tips and impart a frictional force on the
pipette tips, thereby ejecting the array of pipette tips into
respective receptacles in the loading block. In some embodiments,
the tails deflect outwards against the pipette tip before the
pipette tip is dispensed, and/or at the same time the pipette tip
is being dispensed (e.g., the pipette tip is translating), and
sometimes the tails contact the proximal portion of a pipette tip.
In some embodiments, a subset of channels in the distal barrier
plate are surrounded by tails that eject pipette tips of an array
at one time, and another subset of channels in the plate are
surrounded by tails that eject pipette tips of the same array at
another time. A distal barrier plate may include 2, 3, 4, 5, 6, 7,
8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 of such subsets
of channels.
[0025] In some embodiments pertaining to a dispensing device
described in the preceding paragraph, the top surface and/or the
bottom surface is substantial flat or planar. In certain
embodiments, the barrier plate can comprise 2, 3, 4, 5, 6, 7, 8, 9,
10 or more tails. Each channel of the barrier plate can comprise
tails of the same length. In some embodiments, each channel of the
barrier plate can comprise tails of different lengths. Channels
located in the center of the barrier plate can comprise the longest
tails. In some embodiments, channels located in the center of the
barrier plate can comprise the shortest tails. Subsequent channels
concentrically disposed about a central longitudinal axis can
comprise sequentially shorter tails in length in a stepwise manner
in some embodiments. Subsequent channels concentrically disposed
about a central longitudinal axis can comprise sequentially longer
tails in length in a stepwise manner in certain embodiments. In
some embodiments, channels located in the center of the barrier
plate along the X axis can comprise tails of the same length and
channels along the Y axis comprise tails of varying length. In some
embodiments, channels located in the center of the barrier plate
along the Y axis can comprise tails of the same length and channels
along the X axis comprise tails of varying length. In certain
embodiments, channels located in the center of the barrier plate
along the X and Y axes can comprise tails of varying length. Each
channel can comprise an even number of tails in some embodiments,
and in certain embodiments tails directly opposite one another
around a channel can have the same length. Tails directly opposite
one another around a channel can have a different length in some
embodiments, and in certain embodiments, tails adjacent to one
another can have a different length. The tails can be at an
internal angle of about 89.degree. to about 80.degree. from the
bottom surface of the distal barrier plate in some embodiments. In
certain embodiments, tails can be at an internal angle between
88-85.degree., 87-84.degree., 86-83.degree. or 86-85.degree. from
the bottom surface of the distal barrier plate. In some
embodiments, tails can be at an internal angle of about 87.degree.
from the bottom surface of the distal barrier plate. The tails can
be between 0.01 .mu.m-2.0 mm in length in some embodiments, and in
certain embodiments, the tails can be between 0.05 .mu.m-2.0 mm in
length. The tails around a channel are not in the channel in some
embodiments. The actuator can comprise an actuator housing and an
alignment housing both having a clear polymer material to visualize
ejection of the array of multiple pipette tips from the tails of
the barrier member during actuation in some embodiments. The
actuator housing can comprise a telescoping arrangement having
multiple housing elements and where actuation of the actuator
comprises collapsing the multiple housing elements from an extended
state to a collapsed nested state in certain embodiments.
[0026] Certain embodiments are described in the following detailed
description, claims and drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0027] The drawings illustrate embodiments of the invention and are
not limiting. For clarity and ease of illustration, the drawings
are not made to scale and, in some instances, various aspects may
be shown exaggerated or enlarged to facilitate an understanding of
particular embodiments.
[0028] Certain features common to some or all the figures (e.g.,
FIG., or FIGS.) presented herein are identified by a prime symbol
(') after the reference character. For example a feature labeled 14
in one drawing and substantially similar or substantially identical
to a feature in one or more additional drawings, would be labeled
14' in the second and subsequent drawings. In instances where a
figure is not explicitly described, but contains reference
characters containing the prime symbol ('), it will be understood
the description given for the reference character in one figure,
will be substantially identical for the reference character with
the prime symbol.
[0029] FIG. 1 shows an exploded perspective view of an embodiment
of a pipette tip dispensing device.
[0030] FIG. 2 shows an elevation view of an embodiment of a pipette
tip.
[0031] FIG. 3 illustrates a cross section of the pipette tip of
FIG. 2 taken along lines 3-3 of FIG. 2.
[0032] FIG. 4 shows a perspective view of the pipette tip
dispensing device of FIG. 1.
[0033] FIG. 5A is a transverse cross section of the dispensing
device of FIG. 4 taken along lines 5A-5A of FIG. 4, showing a
single column of three nested pipette tips disposed between a
proximal alignment member of the actuator plate and a respective
restrictive aperture of the barrier plate. FIG. 5B shows the view
of FIG. 5A after the actuator has been fully actuated three clicks
to a position where all nested pipette tips have been ejected into
loading blocks and the proximal alignment members are disposed
within respective distal restrictive apertures.
[0034] FIG. 6A shows an enlarged cut-away view in partial section
of a stacked nested array of pipette tips engaged with a proximal
alignment member, distal restrictive aperture and loading block
prior to actuation. FIG. 6B shows the same view as FIG. 6A after
the actuator has been advanced or actuated one click so as to move
the actuator plate towards the barrier plate and eject the distal
most pipette tip of the nested column into the corresponding
aperture of the loading block.
[0035] FIG. 7 shows an elevation view of an embodiment of a
pipettor with a pipette tip engaged with a distal nozzle
thereof.
[0036] FIG. 8 is a perspective view of an embodiment of a loading
block.
[0037] FIG. 9 shows a distal nozzle of a pipettor engaging a
proximal port of a pipette tip disposed in a loading block.
[0038] FIG. 10 shows multiple nozzles of an automated manifold
engaging multiple corresponding pipette tips disposed in a loading
block.
[0039] FIG. 11 shows an elevation view in transverse cross section
of a telescoping embodiment of a pipette tip dispensing device with
the actuator housing assembly in a fully extended state and a full
column of nested pipette tips disposed between the barrier plate
and proximal alignment members.
[0040] FIG. 12 shows the pipette tip dispensing device of FIG. 11
in a compressed state with the telescoping elements of the actuator
housing in a collapsed state.
[0041] FIG. 13A shows a perspective view of a distal barrier plate
with tails pointing in an upward orientation. FIG. 13B shows an
enlarged cut away view of FIG. 13A (see arrows in FIG. 13A)
detailing the tails. FIG. 13C shows a lateral partial profile view
of the tails, where all the tails are the same length. FIG. 13D
shows an enlarged cut away, lateral partial profile view of one
channel, where the orientation of the each tail is in part defined
by an internal angle theta.
[0042] FIG. 14A shows a bottom view of a distal barrier plate with
tails arranged in a nearly perpendicular orientation with respect
to the bottom surface of the plate. FIG. 14A shows X and Y axes
referenced herein. FIG. 14B shows an enlarged cut away view of FIG.
14A (see arrows in FIG. 14A) detailing certain aspects of tails and
their orientation to channels. FIG. 14C shows a lateral profile
view of the tails, where the tails are varied in length.
[0043] FIG. 15A shows a perspective view of an activator plate,
also referred to herein as an actuator plate. FIG. 15B shows a
width side view of an activator plate. FIG. 15C shows a top view of
an activator plate. FIG. 15D shows a length side view of an
activator plate. FIG. 15E shows a bottom view of an activator
plate.
[0044] FIG. 16A shows a perspective view of a distal barrier plate.
FIG. 16B shows a width side view of a distal barrier plate. FIG.
16C shows a top view of a distal barrier plate. FIG. 16D shows a
length side view of a distal barrier plate embodiment configured
with tails of equal length. FIG. 16E shows a bottom view of a
distal barrier plate. FIG. 16F shows a length side view of a distal
barrier plate embodiment configured with tails of different
lengths.
DETAILED DESCRIPTION
[0045] Discussed herein are method and device embodiments for
handling, storage and dispensing of pipette tips used for a variety
of material handling applications. Pipette tips may generally be
engaged with a distal nozzle of a pipettor or similar device in
order to draw and drop liquid slugs in precise amounts. Such tips
may be used for the transfer and handling of liquids for
applications such as titration and dispensing of liquids, DNA
sequencing, cycle sequencing, PCR and other DNA analysis as well as
other liquid handling applications. For many of these applications,
large numbers of samples must be processed in a precise manner and,
as such, a large number of pipette tips are used for such methods.
In order to avoid cross contamination of samples, pipette tips are
typically used only once for each sample being processed. Because
of the large number of samples being processed and the single use
nature of the pipette tips, a large number of pipette tips need to
engaged with pipettor type devices and then removed from those
devices and disposed of.
[0046] Due to such large volume handling and disposal, it is
desirable for some applications to have devices and methods for
pipette tip transfer and loading in arrays of multiple tips from a
single packaging source to avoid the need for disposing of a
package for each array loaded onto a pipettor device. What is also
desirable for some applications are devices and methods for loading
an array of multiple pipette tips without the need to transfer a
separate loading plate from the packaging of the tips which may
cause additional waste for disposal in addition to affecting the
cumulative z-axis height of the pipette tips being loaded. Some
pipette tip dispensing device and method embodiments discussed
herein are directed to the handling, storage and simultaneous
dispensing of a plurality of pipette tips disposed in a regularly
spaced array into a loading plate or block. Some of these
embodiments have the capacity to serially dispense multiple arrays
or pipette tips without transferring loading plates or the need for
handling of individual pipette tips. Some embodiments of pipette
tip dispensing devices discussed herein are also capable of
dispensing arrays of multiple pipette tips accurately and
conveniently without the need to transfer a loading tray from the
packaging of the pipette tips.
[0047] Device and method embodiments described herein provide
several advantages. Device and method embodiments herein allow for
storing, loading or handling of pipette tips, and allow for
convenient loading of pipette tips without the need to transfer a
storage plate that may affect the z-axis location of the top
surface of the loading block into which the pipette tips are
transferred. Device and method embodiments herein also allow for
multiple pipette tips to be loaded simultaneously without the
transfer of a storage plate. Such embodiments also allow for
pipette tips to be stored in a nested configuration, in one or more
nested column arrays for some embodiments, and allow the bottom
pipette tip of each nested column to be conveniently dispensed into
a loading plate or loading block.
[0048] A pipette tip can be of any geometry useful for dispensing
fluids in combination with a dispensing device. Pipette tips
sometimes are available in sizes that hold from 0 to 10
microliters, 0 to 20 microliters, 1 to 100 microliters, 1 to 200
microliters and from 1 to 1000 microliters, for example. The
external appearance of pipette tips may differ, and certain pipette
tips can have a continuous tapered wall forming a central channel
or tube that is roughly circular in horizontal cross section, in
some embodiments. A pipette tip can have any cross-sectional
geometry that results in a tip that (i) provides suitable flow
characteristics, and (ii) can be fitted to a dispenser (e.g.,
pipette), for example. Pipette tips sometimes taper from the widest
point at the top-most portion of the pipette tip (pipette proximal
end or end that engages a dispenser), to a narrow opening at the
bottom most portion of the pipette tip (pipette distal end or end
used to acquire or dispel fluid). In certain embodiments, a pipette
tip wall includes two or more taper angles. The inner surface of
the pipette tip sometimes forms a tapered continuous wall, in some
embodiments, and in certain embodiments, the external wall may
assume an appearance ranging from a continuous taper to a stepped
taper or a combination of smooth taper with external protrusions.
An advantage of an externally stepped taper is compatibility with
pipette tip racks from different manufacturers. The bore of the
top-most portion of the central channel or tube generally is wide
enough to accept a particular dispenser apparatus (e.g., nozzle,
barrel).
[0049] In some embodiments, a pipette tip has (i) an overall length
of about 1.10 inches to about 3.50 inches (e.g., about 1.25, 1.50,
1.75, 2.00, 2.25, 2.50, 2.75, 3.00, 3.25 inches); (ii) a
fluid-emitting distal section terminus having an inner diameter of
about 0.01 inches to about 0.03 inches (e.g., about 0.015, 0.020,
0.025 inches) and an outer diameter of about 0.02 to about 0.7
inches (e.g., about 0.025, 0.03, 0.04, 0.05, 0.06 inches); and
(iii) a dispenser-engaging proximal section terminus having an
inner diameter of about 0.10 inches to about 0.40 inches (e.g.,
about 0.15, 0.20, 0.25, 0.30, 0.35 inches) and an outer diameter of
about 0.15 to about 0.45 inches (e.g., about 0.20, 0.25, 0.30,
0.35, 0.45 inches). In the latter embodiments, the inner diameter
is less than the outer diameter.
[0050] The wall of the distal section of a pipette tip sometimes is
continuously tapered from the wider portion, which is in effective
connection with the proximal section, to a narrower terminus. The
wall of the distal section, in some embodiments, forms a stepped
tapered surface. The angle of each taper in a distal section is
between about zero degrees to about thirty degrees from the central
longitudinal vertical axis of the pipette tip (e.g., about 0, 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 degrees), in certain
embodiments. In some embodiments, the wall of the distal section
forms stepped vertical sections. The wall thickness of a distal
section may be constant along the length of the section, or may
vary with the length of the section (e.g., the wall of the distal
section closer to the proximal section of the pipette tip may be
thicker or thinner than the wall closer to the distal section
terminus; the thickness may continuously thicken of thin over the
length of the wall). The distal section of a pipette tip generally
terminates in an aperture through which fluid passes into or out of
the distal portion. A distal section of a pipette tip may contain a
filter, insert or other material.
[0051] The wall of the proximal section of a pipette tip sometimes
is continuously tapered from the top portion, a narrower terminus.
The top portion generally is open and often is shaped to receive a
pipette tip engagement portion of a dispensing device. The wall of
a proximal section, in some embodiments, forms a stepped tapered
surface. The angle of each taper in the proximal section is between
about zero degrees to about thirty degrees from the central
longitudinal vertical axis of the pipette tip (e.g., about 0, 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 degrees), in certain
embodiments. The wall thickness of a proximal section may be
constant over the length of the section, or may vary with the
length of the proximal section (e.g., the wall of the proximal
section closer to the distal section of the pipette tip may be
thicker or thinner than the wall closer to the top of the proximal
section; the thickness may continuously thicken or thin over the
length of the wall). A proximal section of a pipette tip may
contain a filter, insert or other material.
[0052] In certain embodiments, pipette tips in a pipette tray
comprise one or more of a filter component and/or an insert
component. A filter may be located in any suitable portion of a
pipette tip, and sometimes is located in a proximal portion of a
pipette tip near a pipette tip aperture that can engage a
dispensing device. A filter can be of any shape (e.g., plug, disk;
U.S. Pat. Nos. 5,156,811 and 7,335,337) and can be manufactured
from any material that impedes or blocks migration of aerosol
through the pipette tip to the proximal section terminus, including
without limitation, polyester, cork, plastic, silica, gels, and the
like, and combinations thereof. In some embodiments a filter may be
porous, non-porous, hydrophobic, hydrophilic or a combination
thereof. A filter in some embodiments may include vertically
oriented pores, and the pore size may be regular or irregular.
Pores of a filter may include a material (e.g., granular material)
that can expand and plug pores when contacted with aerosol (e.g.,
U.S. Pat. No. 5,156,811). In certain embodiments, a filter may
include nominal, average or mean pore sizes of about 10, 9, 8, 7,
6, 5, 4, 3, 2, 1, 0.5, or 0.05 micrometers, for example. A section
of a pipette tip also may include an insert or material that can
interact with a molecule of interest, such as a biomolecule. The
insert or material may be located in any suitable location for
interaction with a molecule of interest, and sometimes is located
in the distal section of a pipette tip (e.g., a material or a
terminus of an insert may be located at or near the terminal
aperture of the distal section). An insert may comprises one or
more components that include, without limitation, multicapillaries
(e.g., US 2007/0017870), fibers (e.g., randomly oriented or
stacked, parallel orientation), and beads (e.g., silica gel, glass
(e.g. controlled-pore glass (CPG)), nylon, Sephadex.RTM.,
Sepharose.RTM., cellulose, a metal surface (e.g. steel, gold,
silver, aluminum, silicon and copper), a magnetic material, a
plastic material (e.g., polyethylene, polypropylene, polyamide,
polyester, polyvinylidenedifluoride (PVDF)), Wang resin, Merrifield
resin or Dynabeads.RTM.). Beads may be sintered (e.g., sintered
glass beads) or may be free (e.g., between one or two barriers
(e.g., filter, frit)). Each insert may be coated or derivitized
(e.g., covalently or non-covalently modified) with a molecule that
can interact with (e.g., bind to) a molecule of interest (e.g.,
C18, nickel, affinity substrate).
[0053] FIG. 1 shows an exploded perspective view of an embodiment
of a pipette tip dispensing device 10. The dispensing device
embodiment 10 includes a displacement actuator that has an actuator
housing 12 with a top portion, four sides, and an inner surface.
Sets of regularly spaced detent members 14 are disposed on all four
sides of the housing 12. Each set of detent members 14 on the
actuator housing 12 includes three detent members 14 equally spaced
in a vertical direction. A plurality of proximal alignment members
16 are disposed in a regularly spaced array of 8.times.12 alignment
members 16 on an actuator plate 18 disposed at a top portion of the
actuator housing 12. Each proximal alignment member 16 is
configured to releasably engage and restrict the lateral
displacement of a proximal end of a pipette tip, such as the
pipette tip 20 illustrated in FIGS. 2 and 3.
[0054] An alignment housing 22 which is configured to slide within
the actuator housing 12 includes an outside surface in contact with
the inside surface of the actuator housing 12 in a sliding
arrangement. The alignment housing 22 also includes a plurality of
regularly spaced detent members 24 which are configured to
releasably engage the corresponding detent members 14 of the
actuator housing 12. As such, the detent members 24 of the
alignment housing have a regular spacing that is substantially the
same as the regular spacing of the detent members 14 of the
actuator housing as shown by arrow 15 in FIG. 5A. Also, the detent
members 24 of the alignment housing 22 have a shape that is
configured to releasably engage the detent members 14 of the
actuator housing. The alignment housing 22 has a rectangular
proximal opening with an inside surface which is sized and
configured to engage outer lateral sides of a loading block 26
which is shown disposed within the proximal opening of the
alignment housing 22.
[0055] A distal barrier element in the form of a distal barrier
plate 28 is disposed at a top portion of the alignment housing 22
and lies substantially parallel to the actuator plate 18 of the
actuator. The distal barrier plate 28 includes a plurality of
restrictive apertures 32 which are substantially aligned with
corresponding respective proximal alignment members 16 of the
actuator plate 18 within the actuator housing 12. The actuator
housing 12 is configured to slide relative to the alignment housing
22 to a collapsed state where the proximal alignment members 16
directly engage the restrictive apertures 32 of the distal barrier
plate 28 so as to push the last of a set of nested pipette tips
through the barrier plate and into the respective channels 34 of
the loading block 26 which is disposed below the barrier plate.
[0056] In FIG. 1, a single column of nested pipette tips is shown
disposed between a proximal alignment member 16 and distal
restrictive aperture 32 for purposes of illustration, however, a
column of nested pipette tips may generally be disposed between
each proximal alignment member 16 and corresponding restrictive
aperture 32. The longitudinal axis 36 of each of the pipette tips
20 in the nested array are substantially aligned and coaxial as
shown in FIG. 6A. A shoulder portion 38 of the proximal most
pipette tip is disposed against a proximal end of the adjacent
pipette tip. During typical use, a column of an equal number of
nested pipette tips 20 may be disposed between each of the
respective proximal alignment members 16 and distal restrictive
apertures 32 in a configuration that is the same as or similar to
the configuration of nested tips shown. In addition, any desired
number of columns could be used. The regular spacing of the
proximal alignment members 16, distal restrictive apertures 32, and
columns of nested pipette tips disposed therebetween may be about 1
mm to about 5 mm for some embodiments.
[0057] A specific embodiment of pipette tip 20 is shown in FIGS. 2
and 3, however, pipette tips may have a wide variety of
configurations, dimensions and materials, each of which may be
accommodated for use with any of the dispensing device embodiments
discussed herein. For example, pipette tips may be configured as
filter tips that include one, two, three or more filter elements
disposed within a barrel of the tip in order to block aerosols from
the pipettor device as well as other purposes.
[0058] The pipette tip 20 shown has a generally barrel shaped
configuration which is concentrically disposed about a longitudinal
axis 36 of the pipette tip 20. An inner lumen 40 extends coaxially
along the length of the pipette tip 20 and tapers generally from
the proximal opening of the pipette tip to a smaller distal
opening. The proximal opening at a proximal end 42 of the tip 20
may have an inside surface with a tapered contour that is
configured to engage an outer surface of a distal nozzle of a
pipettor device, such as the pipettor device 44 shown in FIG. 7, in
a sealed and releasable arrangement.
[0059] An outer surface of the proximal end of the pipette tip may
have a rim, shoulder or other structure 46 that forms a major outer
transverse dimension of the tip 20 which is disposed at the axial
position of the pipette tip 20 having the largest transverse
dimension. The barrel shaped configuration may have a generally
round transverse cross section with the major outer transverse
dimension at the proximal end 42 of the pipette tip of about 0.2
inches to about 0.4 inches, more specifically, about 0.25 inches to
about 0.35 inches, for some embodiments. The outer transverse
dimension of the pipette tip may taper to a minor outer transverse
dimension at a distal end of the pipette tip 20 of about 0.02
inches to about 0.05 inches, more specifically, about 0.03 inches
to about 0.04 inches, for some embodiments. The inner lumen may
have a contour and taper that substantially corresponds to the
taper and contour profile of the outer surface. The distal port or
opening at the distal end of the inner lumen of the pipette tip may
have a transverse dimension or diameter of about 0.01 inches to
about 0.03 inches, more specifically, about 0.015 inches to about
0.025 inches, for some embodiments.
[0060] The shoulder portions 38 of the outer surface of some
pipette tip embodiments 20 may have a minor transverse dimension
that will fit within the proximal opening of another similar
pipette tip and a major transverse dimension that is larger than
the proximal opening of a similar pipette tip. With such an
arrangement, the shoulder portion 38 of a first pipette tip thereby
includes a distal surface or feature that may engage a proximal end
or surface of another corresponding second pipette tip that is in
nested engagement with the first pipette tip. The engagement of the
shoulder portion of the first pipette tip with a proximal surface
of the second pipette tip allows the transfer axial force between
the first and second nested pipette tips without engaging the
respective inner and outer tapered surfaces of the tips which might
cause them to bind together making release of the tips from each
other difficult.
[0061] The wall thickness of some embodiments of pipette tips may
be about 0.003 inches to about 0.01 inches and the overall length
of some pipette tip embodiments may be about 1.5 inches to about
3.5 inches, more specifically, about 2 inches to about 3 inches.
Some embodiments of pipette tips may be made of suitable polymers
such as polypropylene, polyethylene, polystyrene, polyurethane and
the like as well as any other suitable polymers. Such polymer
materials as well as others may be configured to allow the proximal
end or portion of the pipette tip to elastically deform or compress
sufficiently to allow passage through the restrictive aperture 32
of the barrier member 28 if sufficient threshold axial force is
applied to a pipette tip 20 engaged with a restrictive aperture 32.
For such embodiments, once the pipette tip 20 has passed through
the restrictive aperture 32, and the inward radial constraint of
the restrictive aperture on the pipette tip has been removed, the
proximal end or portion elastically returns to its original shape.
Such a process may occur with any structure 46 that forms the major
outer transverse dimension of the pipette tip 20.
[0062] Referring again to FIG. 1 as well as FIGS. 4-6, FIGS.
15A-15E and FIGS. 16A-16F, the pipette tip dispensing device 10 is
shown in more detail. The displacement actuator includes the
actuator housing 12 that may be made from a clear, thin rigid
material formed into a substantially rectangular configuration with
an open bottom portion, substantially planar sides that may be
arranged substantially perpendicular to each other and to the top
surface and actuator plate 18 disposed within an upper end of the
housing 12. For some embodiments, the actuator housing 12 may be
made from a thin clear polymer material that is transparent or
translucent and may have a thickness of about 0.005 inches to about
0.05 inches. For some embodiments, the actuator housing 12 may be
made from suitable metals, such as aluminum, or polymers such as
polypropylene, polycarbonate, polyethylene, polystyrene,
polyurethane and the like as well as any other suitable polymers
that may be molded, thermoformed or the like. The housing 12 may
have a thickness that allows for some flexibility or elastic
deformation of the sides or proximal surface upon manual
manipulation but provides sufficient structural strength to
maintain its general shape upon manual manipulation and actuation.
The actuator housing 12 is also sufficiently rigid to be
self-supporting and maintains integrity sufficient to apply
actuation force on the actuator plate 18 and the array of pipette
tips 20 being dispensed through the restrictive apertures 32 of the
barrier plate 28.
[0063] The proximal actuator plate 18 has a plurality of proximal
alignment members 16 disposed substantially in a plane in a
regularly spaced array and each proximal alignment member 16 is
configured to releasably engage and restrict lateral displacement
of a proximal end of a pipette tip 20 that is engaged with the
alignment member 16. The proximal alignment members can be of any
convenient shape suitable for engaging and aligning pipette tips
held in a nested array in the automated pipette tip loading device.
Non-limiting examples of cross-sectional shapes useable for
alignment members in actuator plate embodiments described herein
include circular, square, star-shaped, triangular, cone shape,
hexagonal, octagonal, a polygon shape and the like. An embodiment
of an actuator or activator plate with alignment members having a
star-shaped cross section is illustrated in FIGS. 15A-15E.
[0064] The proximal alignment members 16 may be cone shaped
abutments extending from a distal surface of the actuator plate 18
that may be configured to engage or fit within the proximal port of
corresponding pipette tips to be used with the proximal actuator
plate 18. In certain embodiments, proximal alignment members may
have a star-shaped cross-section (e.g., 3, 4, 5, 6, 7, 8, 9, 10 or
more star members (e.g., prongs) in each abutment), which extend
from a distal surface of the actuator plate (see FIGS. 15A-15E, for
example), and which may be configured to engage or fit within the
proximal port of corresponding pipette tips to be used with the
proximal actuator plate.
[0065] The proximal actuator plate 18 may be made from suitable
metals, such as aluminum, or polymers such as polypropylene,
polycarbonate, polyethylene, polystyrene, polyurethane and the like
as well as any other suitable polymers that may be molded,
thermoformed or the like. The proximal actuator plate 18 and
proximal alignment members 16 may be molded from a monolithic
structure of the same material for some embodiments. The proximal
actuator plate 18 may have a thickness of about 0.05 inches and
about 0.25 inches. The proximal actuator plate 18 may be secured to
an inner proximal surface of the actuator housing and may be
configured with sufficient rigidity to maintain a generally planar
configuration when applying axial force to an array of pipette tips
20 engaged with the proximal members 16 thereof as the pipette tips
are being pushed through the restrictive apertures 32 of the distal
barrier plate 28. For some embodiments, the proximal actuator plate
may be integrally molded or otherwise formed with the actuator
housing 12. Some pipette tip array embodiments of the actuator
plate 18 and barrier member may include 96 pipette tip arrays of
8.times.12 pipette tips spaced about 9 mm apart center to center,
some other embodiments may include 384 pipette tip arrays of
16.times.24 pipette tips spaced about 4.5 mm apart center to
center. Other pipette tip array embodiments may include more or
less pipettes depending on the application.
[0066] The alignment housing assembly includes a substantially
rectangular structure having an outside surface which is configured
to slidingly engage the inside surface of the actuator housing 12.
The alignment housing embodiment 22 shown has four sides formed
from a clear, thin, substantially rigid material that may be
transparent or translucent in order to allow an operator to
visualize a pipette tip loading process. The four sides of the
alignment housing 22 include the regularly spaced detent members 24
which are configured to releasably engage the corresponding detent
members 14 of the actuator housing 12. The detent members 24 have a
regular vertical spacing that is substantially the same as the
regular vertical spacing of the detent members of the actuator
housing. The engagement of corresponding detent members secures the
actuator housing 12 in fixed relation to the alignment housing
until a threshold force applied to one of the housings relative to
the other overcomes the detent engagement. The detent engagement
may be used to facilitate incremental movement between the housings
while maintaining the housings in a mechanically coupled relation
when not in use, during shipment while loaded with nested arrays of
pipette tips or at any other suitable time. The amount of
engagement of the corresponding detent members may be about 0.005
inches to about 0.05 inches for some embodiments. The angle that
the sides of the alignment housing 22 form with the barrier plate
28 may be the same as or similar to the angle the sides of the
actuator housing 12 form with the actuator plate 18. These similar
angles may be configured to facilitate the sliding or telescoping
movement between the inside surface of the sides of the actuator
housing 12 and the outer surface of the sides of the alignment
housing 22.
[0067] The alignment housing 22 may be made from the same thin
clear polymer material as that of the actuator housing 12 and have
a similar dimensional configuration such as a thickness of about
0.005 inches to about 0.05 inches. For some embodiments, the
alignment housing may be made from suitable metals, such as
aluminum, or polymers such as polypropylene, polycarbonate,
polyethylene, polystyrene, polyurethane and the like as well as any
other suitable polymers that may be molded, thermoformed or the
like. The alignment housing 22 may have a thickness that allows for
some flexibility or elastic deformation of the sides or proximal
surface upon manual manipulation but provides sufficient structural
strength to maintain its general shape upon manual manipulation and
actuation and may be self-supporting. In particular, the alignment
housing 22 maintains integrity sufficient to resist actuation force
on an array of pipette tips being dispensed through the restrictive
barrier plate 28 at the top or proximal end of the alignment
housing 22.
[0068] The alignment housing 22 includes a proximal opening 48
which has an inside surface or flange that is configured to engage
an outside surface perimeter of the loading block 26. For some
embodiments, the proximal opening 48 of the alignment housing may
be covered with a thin material, such as a thin polymer material
(not shown) for storage and shipment of the device. Such a cover
material may be configured to be temporarily secured to the
alignment housing with a peelable adhesive bond such that the cover
material may be peeled off just prior to use with a tab or other
extension that a user may grasp. The cover material may be useful
for maintaining the stacked array of pipette tips contained within
the device during shipment as well as preventing contamination of
contained pipette tips.
[0069] In some embodiments, the inside transverse dimensions of the
proximal opening 48 of the alignment housing 22 should be a close
fit with not more than about a 0.005 inch to about a 0.05 inch gap
between the outside surface of the perimeter of the loading block
26 to be used and the inside surface of the proximal opening 48.
This controlled fit may be used to assure that the restrictive
apertures 32 of the barrier plate 28 are properly aligned with the
channels 34 of the loading block 26. It may generally be
undesirable for the outer surface perimeter of the loading block 26
to have snug fit with the inside surface of the alignment housing
22 as this might make removal of the pipette tip dispensing device
from the loading block 26 difficult.
[0070] The substantially planar barrier element in the form of the
barrier plate 28 is disposed at a top portion of the alignment
housing 22 substantially perpendicular to the sides of the
alignment housing and substantially parallel to the actuator plate
18 of the actuator. The barrier plate 28 includes a plurality of
the restrictive apertures 32 in an array which is substantially
aligned with respective proximal alignment members 16 of the
actuator plate 18. The restrictive apertures 32 are configured to
engage an outside surface of a pipette tip, restrict lateral
displacement of a pipette tip and resist axial displacement of the
pipette tip until an axial threshold force is imparted to the
pipette tip. Once the threshold axial force is reached, a pipette
tip 20 may pass through the restrictive aperture and be ejected
into the corresponding loading channel 34 of the loading block 26
disposed below the restrictive aperture 32. As soon as the major
transverse dimension of the pipette tip 20 clears the barrier plate
28, gravitational force on the pipette tip 20 moves the tip 20 into
the channel 34 in a distal or downward direction until the major
transverse dimension or proximal end of the pipette tip registers
on the edge of the channel 34 in the loading block 26.
[0071] The barrier plate 28 may be secured around its perimeter to
an upper edge or rim of the alignment housing by welding, adhesive
bonding or any other suitable method. The barrier plate 28 may have
a thickness and material rigidity sufficient to prevent significant
deformation upon the application of actuation force to the pipette
tips 20 disposed in the plate 28. As such, the barrier plate 28 may
have a thickness of about 0.05 inches to about 0.3 inches, more
specifically, about 0.1 inches to about 0.25 inches. For some
embodiments, the barrier plate 28 may be made from suitable metal,
such as aluminum, or polymers such as polypropylene, polycarbonate,
polyethylene, polystyrene, polyurethane and the like as well as any
other suitable polymers that may be molded, thermoformed or the
like. For some embodiments, the barrier plate 28 may have a length
of about 2 inches to about 6 inches and a width of about 1 inch to
about 3 inches.
[0072] For some embodiments, the restrictive apertures 32 of the
barrier plate 28 include holes through the barrier plate 28 that
may have an inner transverse dimension sized and configured to have
a mechanical fit or engagement having an interference fit with the
major outer transverse dimension 46 of the pipette tips 20 that are
to be used with the device. The spacing of the array of restrictive
apertures 32 may generally be configured to match the spacing and
configuration of the alignment members 16 of the actuator plate 18,
which may also match the configuration of the array of channels 34
in a suitable loading block 26. Such an interference fit requires
that the restrictive aperture 32 have an inner transverse dimension
or diameter that is less than the major outer transverse dimension
46 of the pipette tips.
[0073] This interference fit may be overcome by the application of
a threshold axial force on a pipette tip 20 which is engaged with
the restrictive aperture 32. For some embodiments, the interference
fit is overcome by elastic deformation, deflection or compression
of the proximal end or major transverse dimension portion 46 of the
pipette tip 20 as it is forced through the restrictive aperture 32.
The more interference in the fit and the harder the shore hardness
of the material of the pipette tip 20, the greater the threshold
force required to push the pipette tip 20 through the restrictive
apertures 32. For some embodiments, this interference fit may have
an interference of up to about 0.003 inches, more specifically, up
to about 0.002 inches. For some embodiments, the restrictive
apertures 32 of the barrier plate 28 may have an inner transverse
dimension or diameter of about 1 mm to about 9.1 mm. The
restrictive apertures 32 of the barrier plate 28 may have
substantially parallel sides, be configured with tapered sides,
have chamfered edges or edges with a radius or any other suitable
configuration.
[0074] Vertical spacing between the top of the barrier plate 28 and
the top of the loading block 26, as shown by arrow 52 in FIG. 5A,
may be configured such that a distal end or distal portion of a
pipette tip 20 which is engaged with a restrictive aperture of the
barrier plate 28 is disposed within a hole or channel 34 of a
loading block 26 so long as that loading block is engaged with the
alignment housing 22. In this arrangement, the pipette tips are
preloaded into the holes or channels 34 of the loading block 26.
After being ejected from the barrier plate 28 once a threshold
axial force has been applied them, they will continue down into the
channels 34 of the loading block 26. Such distal tip engagement of
the pipette tips into the channels 34 of the loading block 26
reduces or prevents potential jams or mis-feeds of the pipette tips
after ejection from the restrictive apertures 32 of the barrier
plate 28.
[0075] For some embodiments, the vertical distance between the
bottom of the barrier plate 28 and the bottom of the alignment
housing 22 as well as the vertical spacing between the proximal
actuator plate 18 and the bottom of the actuator housing 12 may be
important. In particular, for some embodiments, these distances may
be selected or otherwise configured such that the actuator housing
12 may be depressed down far enough to allow the last array of
pipette tips 20 engaged directly with the proximal alignment
members 16 of the proximal alignment plate 18 to be forced through
the barrier plate 28 and into a loading block 26, as shown in FIG.
5B before the bottom of the actuator housing 12 contacts the
working surface 50 upon which the loading block 26 and alignment
housing 22 are disposed.
[0076] In use, an array of multiple pipette tips 20 may be
dispensed into a loading block 26, with the pipette tip dispensing
device embodiments discussed herein. For some embodiments, the
dispensing device 10 is provided loaded with a regularly spaced
array of 8.times.12 columns of pipette tips nested with 3 pipette
tips in each column as shown in FIG. 5A and in more detail in FIG.
6A. The nested, regularly spaced array may be disposed between any
or all of the respective proximal alignment members 16 and
corresponding restrictive apertures 32 with a longitudinal axis 36
of each nested column of pipette tips being substantially aligned
and coaxial with the respective proximal alignment members 16 and
restrictive apertures 32.
[0077] The proximal opening 48 of the alignment housing 22 may then
be placed over and engaged with a loading block 26 such that distal
ends of the distal most pipette tips 20 of each column, which are
engaged with restrictive apertures of the barrier member 28, are
disposed within channels 34 of the loading block 26 again as shown
in FIG. 6A. Also, the outer perimeter surface of the loading block
26 is engaged with or otherwise laterally constrained by the inner
surface of the alignment housing 22 to prevent substantial relative
lateral movement between the loading block 26 and the alignment
housing 22. Once the dispensing device 10 is so engaged with the
loading block 26, the actuator may be actuated so as to apply an
axial force on the array of columns of pipette tips 20 engaged with
the restrictive apertures 32.
[0078] For some embodiments, the axial force of the actuation may
be generated by manually applying a downward force on an upper
outside surface of the actuator housing 12. The force on the
actuator housing 12 is then transferred to the actuator plate 18
and proximal alignment members 16 thereof, which, in turn,
transmits the axial force to the nested columns of pipette tips 20.
The manually applied force on the actuator housing 12 is continued
until a threshold axial force is achieved so as to deform the major
transverse portions 46 of the pipette tips 20 engaged with the
restrictive apertures 32 of the barrier plate 28. As the force is
applied, the proximal portions and major transverse dimension
portions 46 of the pipette tips 20 may be elastically deformed and
forced through the restrictive apertures 32 so as to eject the row
or array of pipette tips engaged with the restrictive apertures
into respective channels 34 in the loading block 26 as shown in
FIG. 6B with the proximal major transverse dimension portion 46 of
the pipette tips engaging the top surface of the channels 34 of the
loading block 26.
[0079] Once the distal most array of pipette tips 20 are dispensed
into the loading channels 34 of the loading block 26, the next row
of pipette tips 20 move down into the restrictive apertures 32 of
the barrier plate 28 and come to a stop as the major transverse
dimension portions 46 of those pipette tips 20 engage the
restrictive apertures 32. The downward progress of the actuator
housing 12 and actuator plate 18 is also resisted by the engagement
of corresponding detent members of the actuator housing 12 and
alignment housing 22 at the end of the actuation stroke or step.
The dispensing device 10 may then be lifted from the fully loaded
loading block 26 so as to expose the newly loaded pipette tips 20.
In addition, the loading block 26 may then be transferred to
another location for use of the newly loaded pipette tips 20.
[0080] For dispensing device embodiments having the array of nested
columns of pipette tips disposed therein, this process may be
repeated by re-engaging the alignment housing 22 with empty loading
blocks 26 at the beginning of each loading cycle and the actuator
depressed so as to load a new set of pipette tips 20 into the empty
block. As the last array of pipette tips 20 are ejected from the
barrier plate 28, the proximal alignment elements 16 may be
configured to engage and enter the restrictive apertures 32 of the
barrier plate 28 so as to assure ejection of the final row of
pipette tips 20 from the barrier plate.
[0081] During the dispensing process, if the actuator housing 12
and alignment housing 22 comprise a clear or translucent material,
such as a clear or translucent polymer material, the ejection of
the array of multiple pipette tips 20 from the restrictive
apertures 32 of the barrier member 28 may be visualized during
actuation. For manually actuated processes, the alignment housing
22 of the device 10 may be manually placed over and engaged with
loading blocks 26 as needed. The pipette tip dispensing device 10
may also be manipulated by a robotic positioning device (not shown)
such as a three axis to six axis robotic positioning device that
may be configured to engage the alignment housing 22 with an empty
loading block 22, actuate the actuator of the dispensing device 10,
remove the dispensing device 10 from the loading block 26 that is
newly loaded with pipette tips 20, remove the loaded loading block
26 and replace it with an empty loading block 26 and repeating the
process.
[0082] Once the pipette tips 20 are loaded into the loading block
26 as shown, the pipette tips 20 may then be engaged with a
pipettor device, such as pipettor device 44. FIGS. 8 and 9 show a
loading block 26 with a pipette tip 20 disposed in a loading
channel 34 of the block 26 and a nozzle 54 of a pipettor 44, such
as the pipettor 44 of FIG. 7, engaged with the proximal port of the
pipette tip 20. When the pipettor nozzle 54 is engaged with the
proximal port of the pipette tip 20, the pipettor 44 may then be
used for any of the applications discussed herein as well as any
other suitable applications. Once the pipette tip 20 on the
pipettor device 44 has been used, it may be ejected from the
pipettor device 44 and replaced with a new pipette tip 20 from the
loading block 26 and the process repeated.
[0083] For automated method embodiments, an array 56 of multiple
nozzles 54 of a robotic or automated pipettor device 58 may be
engaged simultaneously with an array of pipette tips 20 as shown in
FIG. 10. Such a loading block 26 may be loaded with the array of
pipette tips 20 with the dispensing device 10 of FIG. 1. Once the
pipette tips 20 disposed on the automated pipettor device 58 have
been used for the intended application, they may be ejected from
the pipettor device 58 and disposed of. A new set of pipette tips
20 may then be loaded onto the nozzles 54 pipettor device 58 from a
freshly filled loading block 26 which has been filled by dispensing
device 10. Such an automated process is facilitated by the use of
the pipette tip dispensing device 10 or other similar embodiments
as the loading blocks 26 may be quickly and conveniently refilled
with a new array of pipette tips 20 without the need to transfer a
loading plate or tray from the pipette tip packaging.
[0084] FIGS. 11 and 12 illustrate an embodiment of a pipette tip
dispensing device similar in many respects to the dispensing device
embodiment 10 of FIG. 1, except that the actuator housing of the
embodiment includes a telescoping configuration that allows for the
storage and dispensing of a greater amount of nested pipette tips
disposed in a regularly spaced array. The dispensing device 60 of
FIGS. 11 and 12 includes an alignment housing 22 that may have
features, dimensions and materials that are the same as or similar
to those of the alignment housing 22 of FIG. 1, including the
details of the barrier plate 28 and proximal opening 48 which may
be configured to engage a loading block 26 in the same manner as
the proximal opening 48 discussed above. The proximal opening or
port 48 may also include a polymer peelable cover sheet over the
proximal port such as the cover discussed above. The telescoping
nature of the actuator housing, however, may be configured to allow
a greater number of pipette tips 20 to be disposed in a nested
stacked array between the respective proximal alignment members 16
and restrictive apertures 32 of the barrier plate 28.
[0085] The particular embodiment of the dispensing device 60 shown
in FIG. 1 is shown with 3 nested, stacked pipette tips 20 and the
embodiment of FIG. 11 is shown accommodating 5 nested, stacked
pipette tips 20 when in an extended state. Although these
embodiments are shown to accommodate arrays of 3 and 5 nested
pipette tips, the respective devices 10 and 60 may also be
configured to accommodate a different number of nested pipette tips
depending the housing configurations and dimension of the pipette
tips 20 being used. Arrays of nested pipette tips stacked from
about 2 pipette tips per stack to about 30 pipette tips per stack
may be used, more specifically, about 3 pipette tips per stack to
about 20 pipette tips per stack, and even more specifically, about
4 pipette tips to about 10 pipette tips, may be used.
[0086] The actuator housing includes a proximal housing member 62
and a distal housing member 64 that is vertically displaceable
within the proximal housing member 62. The distal housing member 64
has no top portion and has an inside surface configured to
slidingly engage the outer lateral surfaces of the alignment
housing 22 in a manner similar to the engagement between the
alignment housing 22 and actuator housing 12 discussed above. FIG.
12 illustrates the pipette tip dispensing device 60 of FIG. 11 in a
collapsed state with all pipette tips 20 having been dispensed from
the device and the proximal alignment members 16 of the proximal
actuator housing 62 engaged with the respective restrictive
apertures 32 of the distal barrier plate 28. The detent members 14
and 24 of the proximal actuator housing 62, distal actuator housing
64 and alignment housing 22 are also engaged in this collapsed
state. The construction of the proximal actuator housing member 62
and distal actuator housing member may have the same or similar
features, dimensions and materials as those of the actuator housing
12 and alignment housing 22 discussed above for some
embodiments.
[0087] A pipette tip unit is arranged in an array of pipette tip
units in some embodiments. Each unit has a plurality of nested
pipette tips, and units are arranged in an array in certain
embodiments. The relative configuration of nested pipette tips
often is determined where a first portion of an inner surface of a
first pipette tip interferes with a second portion of the outer
surface of a second pipette tip nesting in and above the first
pipette tip (e.g., the inner diameter of the first portion is about
equal to the outer diameter of the second portion). Pipette tips
can be dispensed as an array of pipette tips one pipette tip (i.e.,
one level) high. For example, a pipette tip array can fill all the
holes in a loading block. When a device of the present invention is
filled with an array of pipette tip units and actuated, a one-layer
pipette tip array would be ejected into an empty loading block 26,
thus filling it, in some embodiments. Each pipette tip unit
comprises 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or more nested
pipette tips in some embodiments. The pipette tips often are nested
continuously, and there often are no intermediate plates or
intermediate components between the nested pipette tips.
[0088] FIGS. 13 and 14 (see also FIGS. 16A-16F) illustrate an
embodiment of a pipette tip dispensing device distal barrier plate
70 having a plurality of channels 76, where each channel has a
diameter larger than the widest portion of a pipette tip, which can
be the major outer transverse dimension 46 of a pipette tip or the
largest outer diameter of the proximal portion of a pipette tip.
The barrier plate 70 in FIGS. 13 and 14 has a substantially flat
top surface 82, and a substantially flat bottom surface 73 that has
a plurality of tails 74 around some or all of channels 76. The
bossed arrangement of substantially flat surface 73 having a
thickness 79 in conjunction with substantially flat surface 72 is
optional, and surface 73 may be continuous to the perimeter of the
plate in some embodiments with no bossed region. FIG. 13B
illustrates tails 74 extending in a nearly perpendicular
orientation from the flat bottom surface 72. The tails 74 around
each channel 76 contact the pipette tip, and optionally deflect
outwards against the proximal portion of a pipette tip, when a
pipette tip is dispensed and passes by the tails 74, thereby
imparting a frictional force on the pipette tip when it is
dispensed. Distal barrier plate 70 also includes tails 74 with
inner surface 75 and optional pins 71.
[0089] Each channel can have 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12.
13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28. 29
or 30 or more tails. FIGS. 13 and 14 illustrate an embodiment of
the barrier plate having four tails 74 per channel. FIGS. 13 and
16D illustrate embodiments of a barrier plate where each channel of
the barrier plate comprises tails of the same length. FIG. 13B
shows an enlarged view of each channel with tails of the same
length. FIG. 13C shows a profile view of the tails 74 where they
are all of the same length in the barrier plate. FIGS. 14C and 16F
show an example of channels of the barrier plate having tails of
different lengths, where tail 78 is shorter than tail 80. In
certain embodiments, channels located in the center of the barrier
plate can also be the shorter tails, as seen in FIGS. 14C and 16F.
Subsequent channels concentrically disposed about a central
longitudinal axis can have progressively longer tails, also seen in
FIG. 14C. In some embodiments channels located in the center of the
barrier plate can have the longest tails, and in certain
embodiments, subsequent channels concentrically disposed about a
central longitudinal axis can have progressively shorter tails,
which is not shown in FIG. 14C. Downward movement of the pipette
tips within the housing often is achieved by pressure or force, not
gravity in most embodiments, and downward movement often is
actuated by a user. Downward force or pressure often begins with
user-induced activation from the center top of the housing device,
with the pressure or axial force greatest at the vertical center.
The pressure or axial force then spreads peripherally to the side
walls of the housing as well as spreading horizontally,
peripherally to the edges of both activator and distal barrier
plates.
[0090] A user may actuate the device several times, unloading or
ejecting an array of pipette tips from the bottom of the distal
barrier plate each time. Pipette tips may be dispensed until, for
example, the device is empty of pipette tips; insufficient axial
force is placed on the device; a force is applied by a user that
racks the housing, activator plate and/or distal barrier plate such
that pipette tips are not ejected; and/or the actuator housing is
at ground level.
[0091] It has been determined that providing a distal barrier plate
that releases pipette tips in an array at different times is
advantageous. A distal barrier plate in which all channels have the
same frictional profile ejects all tips of an array at the same
time, which requires a particular actuating force by the user or
operator, referred to hereafter as total force or "F.sub.T." A
distal barrier plate in which some channels have a different
frictional profile compared to other channels, however, ejects tips
in an array at different times. Without being limited by theory, a
portion of force F.sub.T first ejects one subset of pipette tips in
the array through channels having a first frictional profile, and
another portion of F.sub.T then ejects a second subset of pipette
tips in the array through channels having a second frictional
profile. Thus, releasing tips in an array at different times
effectively spreads out F.sub.T over time, and effectively reduces
the actuating force required to eject tips of an array at any one
point of time.
[0092] The term "same frictional profile" as used herein refers to
channels in a distal barrier plate that apply the same frictional
force to pipette tips in an array for the same amount of time. The
term "different frictional profile" refers to a channel in a distal
barrier plate that applies a different frictional force and/or
applies the same or different frictional force to a pipette tip for
a different amount of time, as compared to another channel in the
plate.
[0093] In some embodiments, a distal barrier plate includes a
subset of channels that ejects pipette tips at a rate different
than another subset of channels. In certain embodiments, a distal
barrier plate includes 2 to 100 different subsets of channels, each
of which eject a pipette tip of one array at a different time
(e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19,
20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95
different subsets). Thus, a distal barrier plate can include 2 to
100 different subsets of channels, each of which have a different
frictional profile. The time lapse between the time one set of tips
is released from one subset of channels to the time another set of
tips is released from another subset of channels can be between
about 0.00001 seconds to about 5 seconds (e.g., 0.0001, 0.001,
0.01, 0.1, 1 second), and the total time required to eject pipette
tips in an array can vary from about 0.001 seconds to about 5
seconds (e.g., 0.01, 0.1, 1 second). In some embodiments, a distal
barrier plate is provided in which all channels have the same
frictional profile and all dispense pipette tips at the same
time.
[0094] In some embodiments, pipette tips at or near the center of a
distal barrier plate eject first, and pipette tips near the edge of
a distal barrier plate eject last. In certain embodiments, subsets
of channels disposed in a linear and/or radial orientation away
from the center to the periphery of the plate sequentially eject
tips at progressively increasing times.
[0095] In certain embodiments, pipette tips at or near the center
of a distal barrier plate are ejected last, and pipette tips at or
near the edge of a distal barrier plate are ejected first. In such
embodiments, subsets of channels disposed in a linear and/or radial
orientation from the periphery of the plate to the center of the
plate sequentially eject tips at progressively increasing
times.
[0096] Where it is noted herein that a channel applies a particular
frictional force to a pipette tip for particular period of time,
the channel periphery or channel walls may apply a frictional force
to the pipette tip. Often, however, a feature outside a channel
applies a frictional force to the pipette tip (e.g., projections or
tails around a channel in connection with a top and/or bottom
surface of the plate).
[0097] Certain features of a distal barrier plate can apply a
particular frictional force to a pipette tip. For example, channel
features, including but not limited to channel diameter; channel
texture; the presence or absence of one or more projections in the
channel (e.g., connected to a channel interior wall); the shape,
size, length, thickness, width, rigidity, texture, and/or angle of
one or more projections in a channel; or combination of the
foregoing, can affect the frictional force applied to a pipette tip
as it is ejected. Also, the presence or absence of one of more
projections outside a channel (e.g., connected to top and/or bottom
surface of a distal barrier plate); the shape, size, length,
thickness, width, texture and/or angle of one of more projections
outside a channel, or a combination of the foregoing, can affect
the frictional force applied to a pipette tip as it is ejected.
[0098] Any suitable number of projections can be present around or
near a channel, including without limitation about 1 to about 50
projections. Projections can contact one or more surfaces of a
pipette tip, in some embodiments. Projections can contact the
widest portion (e.g., largest diameter portion) of a pipette tip
(e.g., proximal region portion), and sometimes do or do not contact
lower diameter portions of a pipette tip (e.g., distal region
portion). Projections sometimes flex against a portion of a pipette
tip (e.g., proximal region portion) when the pipette tip is
dispensed past the projections. Projections in some embodiments are
elastic, and can return to about the same position after a pipette
tip is ejected. Projections in connection with the top surface or
bottom surface of a distal barrier plate sometimes are referred to
herein as "tails," as described herein.
[0099] Projection or tail length can affect the time at which
pipette tips are ejected. Without being limited by theory, tails
having a relatively longer length apply a frictional force for a
longer period of time and result in a tip ejection time that is
longer than for relatively shorter tails. FIGS. 14A and 14C show
channels located in the center of the barrier plate along the X
axis can have tails of the same length and channels along the Y
axis can have tails of varying length. In some embodiments,
channels located in the center of the barrier plate along the Y
axis can have tails of the same length and channels along the X
axis can have tails of varying length or channels located in the
center of the barrier plate along the X and Y axes comprise tails
of varying length, which is not shown. Channels can have an even or
odd number of tails. For channels having even number of tails, the
tails directly opposite one another around a channel can have the
same length. And in certain embodiments tails directly opposite one
another around a channel can have a different length. Tails
adjacent to one another can also have a different length. The tails
can be between 0.01 .mu.m -2.0 mm in length. The tails can be
between 0.05 .mu.m-2.0 mm in length. The tails can be about 0.01,
0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.12, 0.14,
0.16, 0.18, 0.2, 0.22, 0.24, 0.26, 0.28, 0.30, 0.32, 0.34, 0.36,
0.38, 0.4, 0.42, 0.44, 0.46, 0.48, 0.5, 0.52, 0.54, 0.56, 0.58,
0.6, 0.62, 0.64, 0.66, 0.68, 0.7, 0.72, 0.74, 0.76, 0.78, 0.8,
0.82, 0.84, 0.86, 0.88, 0.9, 0.92, 0.94, 0.96, 0.98, 1.0, 1.2, 1.4,
1.6, 1.8, or 2.0 mm in length, in certain embodiments. A distal
barrier plate in some embodiments may include tails having
different lengths at different channels (e.g., tails around a first
channel have a first length, and tails around a second channel have
a second length). For example, in certain embodiments the length of
tails for each channel progressively increases or decreases (i)
from the center of the X-axis to each end of the X-axis and/or (ii)
from the center of the Y-axis to each end of the Y-axis. As used
herein, the term "progressive" refers to linear, stepwise,
sigmoidal, and exponential, in particular embodiments.
[0100] The internal angle of projections or tails also can affect
the time at which pipette tips are ejected. For example, a
relatively smaller internal angle for tails or projections can
result in a relatively longer time required to eject a pipette tip.
The term "internal angle" as used herein with respect to a tail
around a channel is an angle measured from the midpoint of a
channel at the bottom surface of the plate towards the tail surface
facing the channel (e.g., surface 75 in FIG. 13D), as illustrated
in FIG. 13D as angle theta. For example, an internal angle of
90.degree. from the bottom surface 72 of the distal barrier plate
would be exactly parallel to the Z axis as shown in FIG. 13C. Tails
of the barrier plate often are nearly perpendicular with respect
to, and often are at an internal angle of almost 90.degree. from,
the bottom surface 72 of the distal barrier plate. In some
embodiments, tails 74 are at an internal angle of about 89.degree.
to about 80.degree. from the bottom surface 72 of the distal
barrier plate. Tails can be at an internal angle between
88-85.degree., 87-84.degree., 86-83.degree. or 86-85.degree. from
the bottom surface of the distal barrier plate. Tails are at an
internal angle of about 87.degree. from the bottom surface of the
distal barrier plate in some embodiments. A distal barrier plate in
some embodiments may include tails having different angles at
different channels (e.g., tails around a first channel have a first
internal angle, and tails around a second channel have a second
internal angle). For example, in certain embodiments the internal
angle of tails for each channel progressively increases or
decreases (i) from the center of the X-axis to each end of the
X-axis and/or (ii) from the center of the Y-axis to each end of the
Y-axis.
[0101] Texture of tails or projections can affect the time required
to eject a pipette tip from a distal barrier plate. In some
embodiments, texture can modulates the length, thickness or angle
of a tail. Tails can comprise smooth surfaces in some embodiments,
and in certain embodiments, tails can comprise texture on one or
more surfaces. A tail can be entirely smooth, may be entirely
textured, or may include textured and smooth surfaces, in some
embodiments. A plate can comprise tails that are smooth and some
tails that comprise texture. Tail texture can include, without
limitation, ridges, barbs, grooves, grains, embossed, etches,
pores, pits, lines, scratches, scores, scrapes, cuts, carvings,
incisions and the like. Tail texture can increase frictional force
on pipette tips moving past the tails when dispensed. Texture also
can aid in channeling pipette tips through the tails and into the
loading block 26 (e.g., linear or twisted grooves (e.g., rifled
grooves) extending from a tail top to tail bottom). A distal
barrier plate in some embodiments may include tails having
different textures at different channels (e.g., tails around a
first channel have a first texture that applies a first frictional
force to pipette tips, and tails around a second channel have a
second texture that applies a second frictional force to pipette
tips). For example, in certain embodiments the texture of tails for
each channel progressively increases or decreases the frictional
force (i) from the center of the X-axis to each end of the X-axis
and/or (ii) from the center of the Y-axis to each end of the
Y-axis.
[0102] Tails around a channel often are not in the channel, and the
portion of a tail joined to the distal barrier plate bottom surface
sometimes is co-extensive with the edge of a channel. In some
embodiments, the base portion of a tail joined to the distal
barrier plate bottom surface is displaced a distance from the
channel perimeter that it surrounds, which distance can be a mean,
nominal, average or maximum distance of about 0.001 millimeters to
about 2 millimeters (e.g., the portion of the tail closest to the
channel perimeter that the tail surrounds is offset 0.005, 0.01,
0.05, 0.1, 0.5 or 1 millimeters from the perimeter). The term
"displaced" as used herein with respect to tail orientation refers
to displaced away from channel perimeter such that the tail base is
partially over the channel perimeter, or displaced away from the
channel perimeter so that there is a gap between the channel
perimeter and the tail base on the plate bottom surface equal to
the displaced distance. Thus, the term "surrounds" as used herein
with respect to a tail refers to a tail associated with a channel,
where the tail base is co-extensive with, or displaced towards or
away from, the channel perimeter. For example, tail 74 surrounds
channel 76, and tail 74' surrounds channel 76', but tail 74 does
not surround channel 76', as shown in FIG. 14B.
[0103] Tails described herein generally are not prone to breakage
as pipette tips are dispensed through a distal barrier plate
comprising the tails. Without being limited by theory, the nearly
perpendicular orientation of tails with respect to the bottom
surface of a distal barrier plate contributes to tail stability, as
this orientation requires little flexion of tails to apply a force
to the pipette tips. In certain embodiments, the maximum, mean,
median or nominal tail flexion is about 0.01 degrees to about 10
degrees (e.g., about 0.05, 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9
degrees). The term "flex outward" as used herein refers to a tail
flexing a certain number of degrees added to the internal angle.
For example, a tail that flexes outwards by 2 degree adds 2 degrees
to the internal angle in the flexed state; if the tail in the
unflexed state has an internal angle of 87 degrees, the tail in the
flexed state has an internal angle of 89 degrees. In certain
embodiments, no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 tails, or
portions thereof, are separated from the distal barrier plate for a
set of 480 pipette tips dispensed through the plate.
[0104] A tail may have any convenient shape. A surface of a tail,
can be of a shape that includes without limitation, square,
rectangle, rhombus, parallelogram, circle, oval, arced, curved,
planar, non-planar, and the like. The thickness of a tail can be
continuous or tapered (e.g., tapered towards the top (i.e., in
association with the plate) or bottom (i.e., at the tail terminus)
of the tail).
[0105] In some embodiments, the housing can have an actuator
housing with a top portion, four sides, an inner surface, and a
plurality of regularly spaced detent members disposed on at least
one side of the housing, and an alignment housing with an outside
surface in contact with the inside surface of the actuator housing
in a sliding arrangement, a plurality of regularly spaced detent
members configured to releasably engage the detent members of the
actuator housing and having a regular spacing that is substantially
the same as the regular spacing of the detent members of the
actuator housing, and a proximal opening having an inside surface
configured to engage outer lateral sides of a loading block 26.
[0106] The housing can be made from a polymer material. The polymer
material of the housing can be molded polypropylene, or any
suitable polymer, including, but not limited to polypropylene (PP),
polyethylene (PE), high-density polyethylene, low-density
polyethylene, polyethylene teraphthalate (PET, e.g., bio-PET),
polyvinyl chloride (PVC), polyethylenefluoroethylene (PEFE),
polystyrene (PS), high-density polystryrene, acrylnitrile butadiene
styrene copolymers, crosslinked polysiloxanes, polyurethanes,
(meth)acrylate-based polymers, cellulose and cellulose derivatives,
polycarbonates, ABS, tetrafluoroethylene polymers, corresponding
copolymers and the like, and combinations of the foregoing. The
polymer material of the housing can have a thickness of about 0.005
inches to about 0.05 inches. The actuator housing can have a
telescoping arrangement having multiple housing elements.
[0107] The alignment housing can have an optional flange that
serves as a footing, in some embodiments. The flange can add extra
stability to the housing and can help to ground the housing unit so
that no unwanted horizontal movement can occur.
[0108] The actuator plate 18 can have a member on the top portion
of the actuator that maintains contact with and restricts lateral
displacement of the proximal portion of the pipette tips. The
member can be selected from the group consisting of foam, a raised
grid, a plurality of proximal alignment members 16 and the like.
FIG. 1 shows the proximal alignment members 16 on the top portion
of the activator plate 18. The proximal alignment members can aid
in aligning stacked columns of pipette tips to each channel in the
distal barrier plate, which is associated with each empty hole in a
loading block 26 where an ejected pipette tip is placed. The member
selected can be any material or combination of materials known to
one of skill in the art. The member is placed to prevent unwanted
vertical or horizontal movement of the pipette tips during storage
or activation of the device.
[0109] Static charge can develop on pipette tips during use or
shipping. This static charge can remain on the tips as they reside
in dispensers or trays because there often is no flow or discharge
of the electric charge from the tips to a ground source. Static
charge in/on the tips and other components of a tray or dispenser
may cause some of the tips to repel away from each other and other
tray or dispenser components. This repulsion can result in the tips
arranged in a different orientation than intended, and can
negatively impact interaction with pipette devices (e.g., automated
dispensers).
[0110] In certain embodiments, the pipette tips are in contact with
an electrically conductive member, or a portion thereof, which is
in communication with the exterior of the housing. This contact can
allow static charge from the pipette tips to be discharged. The
contact of an electrically conductive member, or a portion thereof,
sometimes is with top proximal edges of tips, which may involve
direct, indirect, and/or effective communication with the inner
portion of the housing, activator plate, distal barrier plate,
loading block, combination thereof, or component thereof. The
contact sometimes is with the sides of tips which may be in direct,
indirect, and/or effective communication with the housing,
activator plate, distal barrier plate, loading block, combination
thereof, or component thereof. In some embodiments, an electrically
conductive member, or a portion thereof, is in direct, indirect,
and/or in effective communication with the pipette tips which
ultimately aids in discharging the static charge in/on the pipette
tips. The electrically conductive member, or a portion thereof, may
be in effective communication with any component or components of
the device and be in effective communication with the exterior
housing. In certain embodiments, an electrically conductive member,
or a portion thereof, is located in any of components of the device
such as for example, the actuator housing, alignment housing,
activator plate, distal barrier plate, channel, tail and the like,
or a component thereof, or a combination of the foregoing, that is
in effective communication with the pipette tips, and is exposed
through the housing sides or flanges.
[0111] An electrically conductive member may comprise any type of
electrically conductive material known, such as a conductive metal,
for example. Examples of conductive metals include, without
limitation, platinum (Pt), palladium (Pd), copper (Cu), nickel
(Ni), silver (Ag) and gold (Au). The metals may be in any form in
or on the conductive member, for example, such as metal flakes,
metal powder, metal strands or coating of metal. An electrically
conductive member, or portions thereof, may comprise a metal,
polymeric material, foam, film, sheet, foil, salt or combinations
thereof. In some embodiments, a conductive metal foil may be
utilized for one or more components of a pipette tip device (e.g.,
copper-aluminum foil; label adhered to an electrically conductive
tab on exterior of the housing component). The electrically
conductive materials, or portions thereof, may be any material that
can contain movable electric charges, for example such as carbon.
In some embodiments, the electrically conductive member comprises
about 5% to about 40% or more carbon by weight (e.g., 7-10%, 9-12%,
11-14%, 13-16%, 15-18%, 17-20%, 19-22%, 21-24%, 23-26%, 25-28%,
27-30%, 29-32%, 32-34%, 33-36%, or 35-38% carbon by weight). In
certain embodiments, an electrically conductive film is utilized
that includes carbon (e.g., commercially available from Gemini
Plastic Enterprises, Inc., California). An electrically conductive
film in some embodiments contains ethylene vinyl acetate (EVA),
which can impart a supple quality to the film (e.g., about 5% to
about 25% EVA by weight; about 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,
16, 17, 18, 19, 20, 21, 22, 23, 24% EVA). In some embodiments a
conductive tab may be in effective communication with any one or
combination or all of the components of the device and aid in
discharging an electrical charge from the device. A tab often is in
effective communication with a conductive material contacting the
pipette tips and the exterior of the device (e.g., exterior surface
of the housing). The tab may be affixed to one or more portions of
a device (e.g., by an electrically conductive label).
[0112] The term "effective communication" as used herein refers to
direct (e.g., part of the conductive member) or indirect (e.g., via
component not part of the conductive member) in communication with
exterior of the housing. The term "exposure of conductive member"
as used herein may refer to exposure by a reveal in a plate or
member which may extend to the housing exterior or can be free
hanging or may be affixed to an external surface of the housing
and/or loading block. The external surfaces of the housing are for
example the sides or bottom of the actuator or alignment housing.
The external surfaces of the housing are for example the roof or
sides of the housing. The term "affixed" as used herein refer to
attachment for example such as embossed or adhesive.
[0113] The entirety of each patent, patent application, publication
and document referenced herein hereby is incorporated by reference.
Citation of the above patents, patent applications, publications
and documents is not an admission that any of the foregoing is
pertinent prior art, nor does it constitute any admission as to the
contents or date of these publications or documents.
[0114] Modifications may be made to the foregoing without departing
from the basic aspects of the invention. Although the invention has
been described in substantial detail with reference to one or more
specific embodiments, those of ordinary skill in the art will
recognize that changes may be made to the embodiments specifically
disclosed in this application, yet these modifications and
improvements are within the scope and spirit of the invention.
[0115] The invention illustratively described herein suitably may
be practiced in the absence of any element(s) not specifically
disclosed herein. Thus, for example, in each instance herein any of
the terms "comprising," "consisting essentially of," and
"consisting of" may be replaced with either of the other two terms.
The terms and expressions which have been employed are used as
terms of description and not of limitation, and use of such terms
and expressions do not exclude any equivalents of the features
shown and described or portions thereof, and various modifications
are possible within the scope of the invention claimed. The term
"a" or "an" can refer to one of or a plurality of the elements it
modifies (e.g., "a reagent" can mean one or more reagents) unless
it is contextually clear either one of the elements or more than
one of the elements is described. The term "about" as used herein
refers to a value within 10% of the underlying parameter (i.e.,
plus or minus 10%), and use of the term "about" at the beginning of
a string of values modifies each of the values (i.e., "about 1, 2
and 3" is "about 1, about 2 and about 3"). For example, a weight of
"about 100 grams" can include weights between 90 grams and 110
grams. Further, when a listing of values is described herein (e.g.,
about 50%, 60%, 70%, 80%, 85% or 86%) the listing includes all
intermediate and fractional values thereof (e.g., 54%, 85.4%).
Thus, it should be understood that although the present invention
has been specifically disclosed by representative embodiments and
optional features, modification and variation of the concepts
herein disclosed may be resorted to by those skilled in the art,
and such modifications and variations are considered within the
scope of this invention.
[0116] Embodiments of the invention are set forth in the claims
that follow.
* * * * *