U.S. patent application number 10/722654 was filed with the patent office on 2004-07-08 for single channel reformatter.
Invention is credited to Grinberg, Aleksandr, Hatcher, Thomas James.
Application Number | 20040133288 10/722654 |
Document ID | / |
Family ID | 24221769 |
Filed Date | 2004-07-08 |
United States Patent
Application |
20040133288 |
Kind Code |
A1 |
Hatcher, Thomas James ; et
al. |
July 8, 2004 |
Single channel reformatter
Abstract
A single channel reformatter having a syringe that is movable
along a z-axis by a z-positioner. A x-y positioner is capable of
positioning any well of a source plate having a plurality of wells,
and of positioning any well of a destination plate having a
plurality of wells, beneath the syringe. Liquid from a well of the
source plate is aspirated by the syringe and dispensed into one or
more wells of the destination plate. Since the syringe does not
move in the x-y plane, it is advantageously integrated into a wash
system that cleanses it between liquid transfer operations. The
drive element that actuates the syringe to aspirate and dispense
during liquid transfer operations is advantageously used to drive
the wash cycle. In a method according to present invention for
controlling the reformatting operation, well-to-well links are
specified, a preferred execution order for executing the specified
links is determined, and the specified links are executed in the
preferred order.
Inventors: |
Hatcher, Thomas James;
(Burlington Township, NJ) ; Grinberg, Aleksandr;
(Old Bridge, NJ) |
Correspondence
Address: |
DEMONT & BREYER, LLC
SUITE 250
100 COMMONS WAY
HOLMDEL
NJ
07733
US
|
Family ID: |
24221769 |
Appl. No.: |
10/722654 |
Filed: |
November 26, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10722654 |
Nov 26, 2003 |
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09556537 |
Apr 24, 2000 |
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6694197 |
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Current U.S.
Class: |
700/56 |
Current CPC
Class: |
G05B 2219/45092
20130101; G01N 35/109 20130101; G01N 35/1004 20130101; G01N
2035/0091 20130101; G01N 35/028 20130101; G01N 2035/00237
20130101 |
Class at
Publication: |
700/056 |
International
Class: |
G05B 019/18 |
Claims
We claim:
1. An article comprising: a z-positioner operative to move a liquid
transfer vehicle along a z-axis, wherein said liquid transfer
vehicle does not move in a x-y plane; a x-y positioner operative
to: move, in said x-y plane, a first container having a first
plurality of wells; move, in said x-y plane, a second container
having a second plurality of wells; and processing and control
electronics operative to: direct said x-y positioner to align a
well in said first container with said z-axis; and direct said x-y
positioner to align a well in said second container with said
z-axis.
2. The article of claim 1 further comprising a fluid control device
operative to: generate a flow of liquid from said well of said
first container into said liquid transfer vehicle; and generate a
flow of said liquid from said liquid transfer vehicle to said well
in said second container.
3. The article of claim 2 wherein said liquid transfer vehicle is a
syringe.
4. The article of claim 3 wherein said fluid control device is a
linear drive mechanism that is operative to move a plunger of said
syringe.
5. The article of claim 4 wherein said z-positioner is operative to
move said linear drive mechanism along with said plunger and said
syringe during z-positioning operations.
6. The article of claim 2 further comprising a wash system to wash
said liquid transfer vehicle.
7. The article of claim 6 wherein said liquid transfer vehicle is a
syringe, and said syringe is operatively connected to said wash
system.
8. The article of claim 7 wherein said z-positioner is operative to
move said wash system along with said syringe and a plunger of said
syringe during z-positioning operations.
9. The article of claim 2 wherein said processing and control
electronics comprises interactive software through which a user
specifies said well in said first container and said well in said
second container, said interactive software including a graphical
user interface that displays: a first pictorial representation of
said first container and said first plurality of wells; and a
second pictorial representation of said second container and said
second plurality of wells; wherein, said specified well in said
first container is identifiable in said first pictorial
representation as having been specified, and said specified well in
said second container is identifiable in said second pictorial
representation as having been specified.
10. The article of claim 9 wherein said specified well in said
first container is identifiable by being depicted in a first color
in said pictorial representation, while other wells appearing in
said first pictorial representation are not depicted in said first
color.
11. The article of claim 10 wherein said specified wells are
specified using said first and second pictorial
representations.
12. An article comprising: a first linear drive mechanism operative
to move a liquid transfer vehicle along a z-axis, wherein said
liquid transfer vehicle is stationary in an x-y plane defined by an
x-axis and a y-axis; a second linear drive mechanism operative to
move a y-stage along said y-axis; a third linear drive mechanism
that is piggybacked on said y-stage and is operative to move an
x-stage along said x-axis on said y-stage; a fourth linear drive
mechanism operative to generate: aspirating flow into said liquid
transfer vehicle; and dispensing flow out of said liquid transfer
vehicle, wherein said first linear drive mechanism is operative to
move said fourth linear drive mechanism in concert with said liquid
transfer vehicle.
13. The article of claim 12 further comprising a wash system.
14. The article of claim 13 wherein said liquid transfer vehicle is
in fluid communication with said wash system.
15. The article of claim 14 wherein said fourth linear drive
mechanism is operative to cause movement of cleaning fluid through
said wash system.
16. The article of claim 12 wherein said liquid transfer vehicle is
a syringe.
17. The article of claim 16 wherein: said wash system comprises a
wash syringe and a waste syringe; and said fourth linear drive
mechanism is operative to generate: aspirating flow into said wash
syringe and said waste syringe; and dispensing flow out of said
wash syringe and said waste syringe.
18. The article of claim 17 wherein said wash syringe, waste
syringe and liquid transfer vehicle are mechanically linked to said
fourth linear drive system such that: when said waste syringe and
said liquid transfer vehicle are aspirating, said wash syringe is
dispensing, and when said waste syringe and said liquid transfer
vehicle are dispensing, said wash syringe is aspirating.
19. The article of claim 12 wherein said x-stage has a source
container receiver and a destination container receiver that are
each physically configured to receive a micro-titer plate.
20. The article of claim 12 wherein said y-stage is disposed on
first and second linear bearings.
21. The article of claim 12 wherein said x-stage is disposed on
third and fourth linear bearings that depend from said y-stage.
22. An article comprising a wash system, said wash system
comprising: a first conduit in fluid communication with a supply of
cleaning fluid and a wash/waste station; a second conduit in fluid
communication with said wash/waste station and a waste reservoir;
and a drive system for: generating a flow of cleaning fluid from
said supply to said wash/waste station; generating a flow of
contaminated cleaning fluid from said wash/waste station to said
waste reservoir.
23. The article of claim 22 wherein said drive system comprises: a
first syringe having a first plunger; a linear drive means
operatively engaged to said first plunger.
24. The article of claim 23 wherein said first syringe is in fluid
communication with said first conduit.
25. The article of claim 24 wherein said drive system further
comprises: a second syringe having a second plunger, wherein: said
linear drive means is operatively engaged to said second plunger;
and said second syringe is in fluid communication with said second
conduit.
26. The article of claim 25 wherein said first syringe and said
second syringe are physically configured so that said drive system
is operative to generate said flow of cleaning fluid from said
supply to said wash/waste station and to generate said flow of
contaminated cleaning fluid from said wash/waste station to said
waste reservoir at the same time.
27. An article comprising a wash system for cleaning a working
syringe having a working plunger, said wash system comprising: a
first syringe having a first plunger, said first syringe operative
to aspirate cleaning fluid from a supply reservoir and to dispense
it to said working syringe at a wash/waste station; a second
syringe having a second plunger, said second syringe operative to
aspirate contaminated cleaning fluid that is dispensed from said
working syringe at said wash/waste station and to dispense it to a
waste reservoir; and a linear drive mechanism operatively engaged
to said working plunger, said first plunger and said second plunger
to generate aspirating flow and dispensing flow in said working
syringe, said first syringe and said second syringe.
28. The article of claim 27 wherein said working syringe, said
first syringe and said second syringe are configured so that when
said linear drive mechanism generates aspirating flow in said
working syringe and said second syringe, dispensing flow is
generated in said first syringe.
29. The article of claim 28 further comprising: a first conduit in
fluid communication with said supply reservoir and a first check
valve; a second conduit in fluid communication with said first
check valve, a second check valve and said first syringe; a third
conduit in fluid communication with a second check valve and said
wash/waste station; wherein, when dispensing flow is generated in
said second syringe, said third check valve closes and said fourth
check valve opens placing said second syringe in fluid
communication with said waste reservoir; and when aspirating flow
is generated in said second syringe, said third check valve opens
and said fourth check valve closes placing said second syringe in
fluid communication with said wash/waste station.
30. The article of claim 29 further comprising: a fourth conduit in
fluid communication with said wash/waste station and a third check
valve; a fifth conduit in fluid communication with said third check
valve, said second syringe and a fourth check valve; a sixth
conduit in fluid communication with said fourth check valve and
said waste reservoir; wherein when aspirating flow is generated in
said second first syringe, said first check valve opens and said
second check valve closes placing said first syringe in fluid
communication with said supply reservoir; and when dispensing flow
is generated in said first syringe, said first check valve closes
and said second check valve opens placing said first syringe in
fluid communication with said wash/waste station.
31. The article of claim 27 further comprising a x-y positioner
operable to move objects in contact therewith in an x-y plane.
32. The article of claim 31 further comprising a z-positioner
operable to move said working syringe along a z-axis.
33. A method for washing a liquid transfer vehicle comprising:
aspirating cleaning fluid into a first receiver while, at the same
time: dispensing contaminated cleaning fluid from said liquid
transfer vehicle; and dispensing contaminated cleaning fluid from a
second receiver; and dispensing said cleaning fluid from said first
receiver while, at the same time: aspirating said cleaning fluid
into said liquid transfer vehicle; and aspirating contaminated
cleaning fluid into said second receiver.
34. A method for operating a single channel reformatter ("SCR"),
comprising: specifying a group of source-to-destination links, each
said link indicative of a source well from which liquid is removed
and indicative of a destination well that receives the removed
liquid; determining a preferred execution order for said
source-to-destination links; and executing said
source-to-destination links in said preferred execution order by
removing liquid from said indicated source well and delivering it
to said indicated destination well for each specified
source-to-destination link.
35. The method of claim 34 wherein said step of executing further
comprises: obtaining spatial coordinates for said
source-to-destination links; and converting said spatial
coordinates into actuator control information.
36. The method of claim 35 wherein said step of executing further
comprises actuating positioners within said SCR using said actuator
control information.
37. The method of claim 36 wherein said step of executing further
comprises: positioning an indicated source well at a specified
location in an x-y plane by actuating an x-y positioner; aspirating
said liquid from said indicated source well; positioning an
indicated destination well at said specified location in said x-y
plane by actuating said x-y positioner; and dispensing said
aspirated liquid into said indicated destination well.
38. The method of claim 37 wherein said step of dispensing further
comprises: aspirating cleaning fluid into a first syringe; and
dispensing contaminated cleaning fluid from a second syringe.
39. The method of claim 34 wherein said step of determining further
comprises sequencing said source-to-destination links such that a
destination well of a subsequent source-to-destination link is the
closest well to a destination well of a previous
source-to-destination link.
40. The method of claim 34 wherein said step of specifying further
comprises forming an array of source-to-destination links, wherein:
said array has a size equal to a number of destination wells in a
destination container, and said specified group of
source-to-destination links is a subset of said array of
source-to-destination links.
41. The method of claim 40 wherein said step of specifying further
comprises activating the source-to-destination links in said array
that correspond to said group of source-to-destination links.
42. The method of claim 41 wherein said step of specifying further
comprises, for each activated source-to-destination link:
specifying a row and a column indicative of a position of said
indicated source well; specifying a row and a column indicative of
a position of said indicated destination well; and specifying said
determined execution order.
43. The method of claim 42 wherein said step of specifying further
comprises using a graphical interface whereby: said row and column
of said indicated source well is specified via a pictorial
representation of a source container; and said row and column of
said indicated destination well is specified via a pictorial
representation of said destination container.
Description
FIELD OF THE INVENTION
[0001] The present invention relates to an article for handling
small volumes of liquid. More particularly, the present invention
relates to an article capable of transferring liquid, on a
well-to-well basis, from a source container having a first format
or configuration (e.g., a 96-well micro-titer plate, a vial, etc.)
to a destination container having a second format (e.g., a
1536-well micro-titer plate).
BACKGROUND OF THE INVENTION
[0002] Advances in the field of combinatorial chemistry, high
throughput screening and genomics research have pushed liquid
handling capabilities of conventional devices and instrumentation
to the limit with regard to high-speed handling of micro-volumes of
liquid (i.e., from 0 to about 2 microliters). Specifically, many of
the techniques used in such fields require aspirating liquid from
and dispensing liquid into micro-titer plates or other containers
configured to retain very small quantities of liquid.
[0003] Progress in the aforementioned fields is generating a need
to miniaturize assay format from, for example, the common 96-well
micro-titer plate (6.5 mm well diameter) to 384-well plates (3.5 mm
square wells) and to state-of-the-art 1536-well plates (1.3 mm well
diameter). With these and other assay formats in use, situations
arise wherein liquid must be transferred between plates having
different formats. The usual application is transferring liquid
from a relatively lower density format, such as a 96-well plate, to
a relatively higher density format, such as 384- or 1536-well
plates. This transfer of liquid between plates having different
formats is referred to as "reformatting."
[0004] Tools are available for en masse reformatting. En masse
reformatting is when the contents of groups of wells or even all
the wells of a plate having a first format are transferred, in a
single operation, to the wells of a plate having a second format.
The devices for doing such en masse reformatting typically use a
plurality of syringes (e.g., 8 syringes or 96 syringes are common)
that aspirate the contents of the wells of, for example, a 96-well
plate, and dispense the aspirated liquid into the wells of higher
density plates.
[0005] Of late, there has been interest in reformatting on a
well-by-well basis. In other words, rather than en masse
reformatting, a need has arisen to transfer the contents of a
particular well in a source plate to a particular well in a
destination plate. The prior art offers little in the way of
technology for this application.
[0006] One option, at least in theory, for well-to-well
reformatting is to reformat manually using a pipette. In practice,
this is impractical if not impossible. Aside from an inability to
achieve a sufficient throughput rate for commercial scale
operation, it is probably beyond the capabilities of a human to
accurately or repeatedly pipette liquid into the 1.3 mm wells of a
1536 well plate.
[0007] Another solution in the prior art for well-to-well
reformatting is to use a single pipette head that is attached to an
x-y-z-positioner, such as is described in U.S. Pat. No. 4,979,093
("the '093 patent") assigned to Cavro Scientific Instruments. The
"single channel" (i.e., one pipette) arrangement for dispensing
that is described in the '093 patent is depicted herein in FIG.
1.
[0008] Arrangement 100 depicted in FIG. 1 includes two variable
length arms 102 and 104 that are connected to hinge 106 and to
respective pivots 108 and 110. Stepper motors (not shown) that are
disposed within pivots 108 and 110 change the length of arms 102
and 104 via friction drive wheels and pinch rollers (not shown).
Storage reels (not shown) that are disposed in pivots 108 and 110
accommodate changes in the length of arms 102 and 104. Changing the
length of the arms causes movement in the x-y plane.
[0009] Receiver 107, which is connected to arms 102 and 104,
engages pipette 124. Pipette 124 is operatively connected to
z-motion controller 116 via an "actuator/flow tube" (not shown)
that is disposed within guide tube 114. The actuator/flow tube
slides within actuation guide 114 when actuated by z-motion
controller 116. Such sliding movement of the actuator/flow tube
causes pipette 124 to move along the z-axis (i.e., vertically).
[0010] The actuator/flow tube is also connected to fluid dispenser
118. Fluid dispenser 118 is operative to cause pressure changes
within the actuator/flow tube. Negative relative pressure enables
pipette 124 to aspirate fluid, such as from wells 128 in source
plate 126. Conversely, positive relative pressure enables pipette
124 to dispense aspirated fluid, such as into wells 132 in
destination plate 130.
[0011] Source plate 126 and destination plate 130 are registered in
a known position on a stationary platform (not shown). The x-y-z
coordinates of any well 128 in source plate 126 and the x-y-z
coordinates any well 132 in destination plate 130 can therefore be
determined. To aspirate from well 128A in source plate 126 and then
dispense the aspirated liquid into well 132-19 in destination plate
130, computer 120 transmits the corresponding x-y-z coordinates of
the source and destination wells to controller 122. Controller 122
converts the coordinates into motor control information that drives
the motors (not shown) that control the arms 102 and 104 and the
z-motion controller 116.
[0012] There are a number of shortcomings or problems with the
apparatus described in the '093 patent. In particular, the
positioning operation is relatively slow and disadvantageously
exhibits characteristically low positioning and dispensing accuracy
since all major liquid dispensing functions are operated on a
moving, cantilevered liquid carrier (i.e., the pipette).
[0013] Moreover, this device introduces inefficiency (i.e., time
delays) as a result of the manner in which a series of transfers
are effected. That is, liquid transfers are typically sequenced
without regard to the relative positions, in successive cycles, of
the source and destination wells.
[0014] Furthermore, it will be appreciated that the syringe of a
reformatter must be washed between dispenses to avoid possible
cross contamination. Prior art reformatters and liquid dispensers
in general have very inefficient wash cycles. In particular, in
such devices, the working pipette is typically transported to and
from a wash station, increasing the operating-washing-operating
cycle time. Moreover, wash operations require internal and external
washing of the working pipette, so that the washing operation
creates a substantial waste problem in view of the number of washes
involved and the relatively wasteful manner in which wash solution
is used.
[0015] A need therefore exists for an improved single channel
reformatter.
SUMMARY OF THE INVENTION
[0016] The present invention provides, in some embodiments, a
single channel reformatter that avoids the drawbacks of the prior
art. In particular, the present reformatter is fast and has very
high positioning and dispensing accuracy. Such speed and accuracy
is achieved, in part, by disposing the source and destination
plates on a x-y stage. Rapid and precise motion is more readily
obtained by moving the plates on a x-y stage than by moving a
pipette at the end of a cantilevered arrangement as in the prior
art.
[0017] Moreover, in some embodiments of the present invention, the
liquid transfer vehicle (i.e., pipette, syringe, etc.) is limited
to z-axis motion and, in fact, is mechanically de-coupled from the
x-y stage. A repeatable, accurate dispensing operation is more
readily obtained with a syringe, etc., that is stationary in the
x-y plane than with one that is moving in three dimensions at the
end of a cantilevered arrangement as in the prior art.
[0018] In a further embodiment, the present invention provides an
efficient wash system that advantageously operates between
successive plate-to-plate transfer operations (hereinafter "normal
liquid transfer operations" or "working cycle"). Since, in
accordance with the present teachings, the liquid transfer vehicle
does not travel in the x-y plane during the working cycle, it can
be, and advantageously is, integrated directly into such a wash
system. In such an integrated system, no time is lost, as with
prior art dispensers, in moving the liquid transfer vehicle to a
wash station and back again for the subsequent working cycle.
[0019] In some embodiments, the wash system comprises two
syringes--a wash syringe and a waste syringe--in addition to the
liquid transfer vehicle. In such embodiments, the liquid transfer
vehicle is advantageously configured as a syringe (hereinafter the
"working syringe"). The three syringes are in fluidic communication
with one another and with supply and waste reservoirs. Further, the
three syringes and their plungers cooperate mechanically with a
single drive mechanism such that a "stroke" of the drive aspirates
(dispenses) the working syringe and the waste syringe while, at the
same time, the wash syringe is dispensed (aspirated). Moreover, in
some embodiments, the drive element that actuates the plungers
during the wash cycle is used during normal liquid transfer
operations.
[0020] The present invention also provides a method for controlling
the reformatting operation. The method advantageously comprises:
(1) specifying well-to-well links, (2) determining a preferred
execution order for executing the specified links thereby enhancing
reformatting efficiency, and (3) executing the specified links in
the preferred order. In some embodiments, the preferred execution
order sequences links based on the relative locations of
"destination wells" (i.e., wells that receive liquid from the
source plate) in successive cycles.
BRIEF DESCRIPTION OF THE DRAWINGS
[0021] FIG. 1 depicts an arrangement for single channel
reformatting in the prior art.
[0022] FIG. 2 depicts a conceptual or figurative view of an
illustrative embodiment of a single channel reformatter in
accordance with the present invention.
[0023] FIG. 3 depicts a specific embodiment of the reformatter
depicted in FIG. 2.
[0024] FIG. 4 depicts the x-y positioner of the single channel
reformatter of FIG. 3.
[0025] FIG. 5 depicts a conceptual or figurative view of an
illustrative embodiment of a z-positioner for use in conjunction
with the single channel reformatters of FIGS. 2 and 3.
[0026] FIG. 6 depicts the z-positioner of FIG. 5 as well as a
syringe drive for causing aspirating and dispensing action in the
working syringe.
[0027] FIG. 7 depicts an illustrative embodiment of a wash system
in accordance with the present teachings.
[0028] FIGS. 8A-8C depict the position of the plunger and the
direction of its movement within each of the three syringes
comprising the illustrative wash system of FIG. 7.
[0029] FIG. 9 depicts a method for operating the present single
channel reformatter.
[0030] FIG. 10 depicts processing and control electronics for
controlling the various positioners and drives used in conjunction
with the present single channel reformatter.
[0031] FIG. 11 depicts an illustrative graphical user interface for
use in conjunction with the present single channel reformatter.
[0032] FIGS. 12 and 13 depict an illustrative methodology for
tracking specified links using the graphical user interface of FIG.
11.
[0033] FIG. 14 depicts an illustrative data structure for
organizing link data.
DETAILED DESCRIPTION
[0034] The illustrative embodiments of the present invention that
are described herein and depicted in the accompanying drawings are
directed to a single channel reformatter. This Detailed Description
begins with a description of the functional elements of such a
single channel reformatter. This approach is useful for pedagogical
purposes in that it provides increased clarity of presentation and
generality of description.
[0035] The description of functional elements is followed by a
description of several specific structural embodiments. It should
be understood that the specific structural embodiments are provided
by way of illustration, not limitation. Moreover, the principles,
apparatuses and methods described in this Specification have
applicability beyond the illustrated reformatting application. For
example, a wash system and x-y-z positioning system disclosed
herein may suitably be used to improve the operation of a variety
of liquid-handling apparatuses. And, with modifications that are
within the capabilities of those skilled in the art, the
principles, apparatus and methods described herein are readily
extended to applications other than liquid handling. Such
variations and modifications are within the contemplated scope of
the present invention.
[0036] FIG. 2 depicts an illustrative single channel reformatter
("SCR") 200 in accordance with the present teachings. Illustrative
SCR 200 includes x-y positioner 201, z-positioner 206, optional
integrated wash station 208, liquid transfer vehicle 210, fluid
control device 212, and processing and control electronics 214,
interrelated as shown.
[0037] Z-positioner 206 is operable to move liquid transfer vehicle
210 upwardly and downwardly (i.e., along the z-axis) as directed by
processing and control electronics 214. The term "liquid transfer
vehicle," as used herein, means syringe, pipette, capillary tube,
nozzle or like element suitable for delivering (possibly in
conjunction with an element for causing aspirating or dispensing
flow) a desired amount of liquid at a desired location. In the
illustrated embodiments, the liquid transfer vehicle is a syringe,
and will henceforth be referred to as "working syringe 210."
Working syringe 210 is moved downwardly, for example, in
preparation for dispensing liquid into a container positioned
beneath it, and moved upwardly to allow that container to be moved
away to allow another container to take its place.
[0038] The x-y positioner 201 comprises x-y drive 204 that is
operable, when actuated, to precisely and accurately move x-y stage
202 in the x-y plane. In the illustrated embodiment, x-y stage 202
comprises a surface that is suitable for receiving source container
250 from which liquid is aspirated. Stage 202 is also suitable for
receiving destination container 260 into which the aspirated liquid
is dispensed. In the embodiments described herein, source container
250 is a micro-titer plate having a plurality of wells 152 and
destination container 260 is a micro-titer plate having a plurality
of wells 162. It should be understood, however, that other types of
containers may suitably be used in conjunction with the present
invention.
[0039] With source plate 250 and destination plate 260 disposed on
x-y stage 202, x-y positioner 201 is operable to: (1) position any
of the wells 152 of plate 250 under working syringe 210 so that
liquid contained in such wells can be aspirated into working
syringe 210, and (2) position any of the wells 162 of plate 260
under working syringe 210 so that liquid that has been aspirated
into syringe 210 can be dispensed into such wells.
[0040] To perform well-to-well liquid transfer operations, the
spatial location of each well must be known. To that end, x-y stage
202 has physical adaptations (not shown in FIG. 2) for receiving
plates 250 and 260 at predetermined locations. Given a particular
plate format (e.g., 96-well, 384-well, etc.) and the location of
the plate at either the source plate position or at the destination
plate position on x-y stage 202, the spatial location of each well,
in terms of x, y and z coordinates, is readily determined.
[0041] When appropriately positioned in a specified well 152 in
source plate 250 by the action of positioners 201 and 206, a
suction (i.e., negative relative-pressure) is developed in working
syringe 210 to aspirate a desired amount of liquid from that well.
After aspirating the liquid, working syringe 210 is moved
vertically (i.e., along the z-axis) out of the well. The x-y stage
202 is then advanced to move a specified well 162 in destination
plate 260 in to position beneath working syringe 210. Working
syringe 210 then moves downwardly under the action of z-positioner
206. Once in position in well 162, the fluid within working syringe
210 is dispensed.
[0042] The aspirating and dispensing ("fluid control") functions of
syringe 210 are accomplished via fluid control device 212. The term
"fluid control device," as used herein, means pump, vacuum pump,
ejector, or other arrangement capable for generating aspirating or
dispensing flow through the liquid transfer vehicle (e.g., working
syringe 210). Since, in the illustrated embodiments, a syringe (as
opposed to a pipette, etc.) is used as the liquid transfer vehicle,
the fluid control functions are advantageously implemented by
simply drawing the plunger away from the bottom of body of the
syringe, or pushing it towards the bottom of the body of the
syringe. Thus, the meaning of the term "fluid control device" also
encompasses a mechanism suitable for moving the plunger in the
aforementioned fashion. In recognition of the fact that the
illustrated embodiments depict a syringe as the liquid transfer
vehicle, the fluid flow controller will henceforth be referred to
as "syringe drive 212." The term "syringe drive," as used herein,
thus refers to a mechanism suitable for moving the plunger in the
aforementioned fashion. Those skilled in the art will recognize
that many mechanisms are suitable for such service. By way of
illustration, not limitation, the embodiments depicted herein
utilize a linear drive mechanism for this purpose. As used herein,
the term "linear drive mechanism" refers to any mechanism capable
of moving an object in linear motion.
[0043] Z-positioner 206, x-y positioner 201 and syringe drive 212
are actuated by processing and control electronics 214. The
processing and control electronics, which is capable of performing
the functions described below, is suitably implemented using either
shared or dedicated hardware, including, without limitation,
hardware capable of executing software.
[0044] Provided with "link data" specified by a user (e.g.,
transfer liquid from the well located in the source plate at row 2,
column 7 to destination well (15, 20), etc.), the spatial
coordinates of the wells involved in the transfer, and several
other control parameters described later, processing and control
electronics 214 is operable to:
[0045] (1) actuate x-y positioner 201 to move a well 152 into
position under syringe 210;
[0046] (2) actuate z-positioner 206 to lower working syringe 210
into well 152;
[0047] (3) actuate syringe drive 212 to aspirate liquid from well
152 into working syringe 210;
[0048] (4) actuate z-positioner 206 to raise working syringe 210
out of well 152;
[0049] (5) actuate x-y positioner 201 to move a well 162 into
position under syringe 210;
[0050] (6) actuate z-positioner 206 to lower working syringe 210
into well 162;
[0051] (7) actuate syringe drive 212 to dispense liquid from
syringe 210 into well 162; and
[0052] (8) actuate z-positioner 206 to raise working syringe 210
out of well 162.
[0053] To the extent that different fluids are being handled in
subsequent liquid handling cycles, cross contamination will occur
unless working syringe 210 is washed. To that end, working syringe
210 is advantageously washed via wash system 208 after an
aspirating/dispensing cycle. Wash station 208 advantageously washes
the inside and the outside of working syringe 210 to substantially
reduce the risk of cross contamination. Processing and control
electronics 214 controls the wash operation.
[0054] As already discussed, working syringe 210 is advantageously
not moved in the x-y plane. As a consequence, in some embodiments
of the present invention, working syringe 210 is incorporated
directly into wash system 208. A first benefit of such
incorporation is that time is saved by not having to transfer
working syringe 210 to a wash station and back again. A second
benefit of such incorporation is that, when wash station 208 is
appropriately configured, syringe drive 212 advantageously provides
both the fluid control function during normal liquid transfer
operations and also drives the wash station operations. An
illustrative embodiment of wash system 208 and its workings is
described later in this Specification.
[0055] This Specification continues with a description of FIGS.
3-14, which provide illustrative structural details for the
functional description provided above. Structures depicted in these
Figures will be cross-referenced, as appropriate, to the more
functional representations provided in FIG. 2.
[0056] FIG. 3 depicts an embodiment of SCR 200. The various
positioning, dispensing and wash structures that comprise SCR 200
are advantageously anchored by a frame comprising base plate 320,
back plate 322, left side 324 and right side 326, interrelated as
shown in FIG. 3. Base plate 320 provides support for the x-y
positioner 201 and back plate 322 provides support for z-positioner
206 and wash system 208. Left side 324 and right side 326 support
back plate 322.
[0057] The x-y positioner 201, which, for the sake of clarity, is
depicted sans z-positioner 206 and wash station 208 in FIG. 4,
comprises an x-positioner "piggybacked" on a y-positioner. The
y-positioner includes y-plate or y-stage 436 and two linear
bearings 432 and 434 that are disposed on respective bearing
spacers 428 and 430. The bearing spacers 428 and 430, which are
attached to base plate 320 near the edges of the long sides
thereof, raise linear bearings 432 and 434 (and y-plate 436) above
base plate 320 to allow room for underlying y-drive 438 and the
x-drive (not shown).
[0058] Slides 442 are mounted on the underside of y-plate 436 so
that they engage linear bearings 432 and 434. Slides 442 promote
low-friction movement of y-plate 436 over linear bearings 432 and
434. Y-drive 438 controls the movement of y-plate 436 along the
linear bearings. In the illustrated embodiment, y-drive 438 is
configured as a linear drive mechanism. The particular linear drive
mechanism depicted comprises y-stepper motor 440 that drives a ball
screw assembly (not shown in FIG. 4) in well-known fashion.
Y-stepper motor 440 is attached to base plate 320 and the ball
screw assembly is engaged to the underside of y-plate 436. Y-plate
436 is driven along linear bearings 432 and 434 along the y-axis as
y-stepper motor 440 turns, as dictated by processing and control
electronics 214 (FIG. 2).
[0059] Linear bearings 432, etc., slides 442, etc., and the ball
screw assembly are available from NSK Corporation of Schaumberg,
Ill. Machined parts, such as bearing spacers 428, etc., can be
fabricated to specification by Manheim Corporation of Collegeville,
Pa. Stepper motor 440 is available from Applied Motion Products of
Watsonville, Calif.
[0060] The x-positioner, which is piggybacked on the y-positioner,
includes x-plate or x-stage 448 and two linear bearings 444 and 446
that are disposed near the edges of the long sides of y-plate 436.
Slides 450 are mounted on the underside of x-plate 448 so that they
engage linear bearings 444 and 446 to facilitate low-friction
movement of x-plate 448. The x-drive (not depicted) controls the
movement of x-plate 448 along linear bearings 444 and 446. In some
embodiments, the x-drive is configured as a linear drive mechanism
(not shown), such as the combination of a stepper motor driving a
ball screw assembly.
[0061] As previously described, x-plate 448 has physical
adaptations for receiving source containers 250 and destination
containers 260 at predetermined locations. In the illustrated
embodiment, the containers 250, 260 are micro-titer plates, and the
physical adaptations are guides 452 and 454 that define source
plate receiver 456 and guides 458 and 460 that define destination
plate receiver 462, both appropriately sized and shaped for
receiving micro-titer plates. In other embodiments (not shown), the
guides are movable such that the size of the receiver can be
changed to accommodate containers other than plates. In still other
embodiments, the guides are replaced with various clamping devices
as may be appropriate for receiving certain types of liquid
containers.
[0062] Illustrative z-positioner 206 is depicted, sans x-y
positioner 201, in FIGS. 5 and 6. Z-positioner 206 is depicted, in
the illustrative embodiment, as a linear drive mechanism. The
particular linear drive mechanism shown comprises z-stepper motor
570 driving ball screw assembly 572.
[0063] As depicted in FIG. 5, working syringe 210 is secured to
frame 578, which, in turn, is operatively engaged to ball screw
assembly 572. Specifically, in the illustrated embodiment, screw or
shaft 574 receives frame 578 in sliding engagement above ball nut
576. Frame 578 is also slidingly engaged (via slides 580 that
depend from frame 578) to linear bearing 582, which is itself
attached to back plate 322. As a consequence, frame 578 slides over
linear bearing 582 along direction vector 581 (i.e., along the
z-axis) as urged by ball nut 576 on screw 574 under the action of
z-stepper motor 570.
[0064] As previously mentioned, in some embodiments of the present
invention, working syringe 210 is integrated into wash system 208.
In those embodiments, it is advantageous to mechanically link wash
system 208 to frame 578 so that appropriate elements of wash system
208 move in concert with working syringe 210. In other words, as a
result of such a connection, there is no relative motion between
wash system 208 and working syringe 210. Such a mechanical link is
depicted figuratively in FIG. 5.
[0065] FIG. 6 depicts z-positioner 206 and syringe drive 684
disposed on back plate 322. Syringe drive 684 provides fluid
control functions (i.e., aspirating and dispensing) for working
syringe 210. Syringe drive 684 can be, for example, a linear drive
mechanism like the x-, y- and z-drives previously described. In the
illustrated embodiment, syringe drive 684 comprises s-stepper motor
686 and ball screw assembly 688.
[0066] Syringe drive 684 operatively engages plunger 211 of working
syringe 210. In particular, in the illustrated embodiment, coupling
member 694 engages plunger 211 of working syringe 210 while screw
690 receives coupling member 694 in sliding engagement above ball
nut 692. As a result of such engagement, coupling member 694 and
plunger 211 are moved along direction vector 696 (i.e., along the
z-axis) responsive to movements of ball nut 692 on screw 690 under
the action of s-stepper motor 686. Coupling member 694, and any
other structural members (e.g., plates, etc.), may suitably be
formed from anodized aluminum.
[0067] As previously indicated, in some embodiments, syringe drive
684 is advantageously used to drive wash systems operations, as
well as normal liquid transfer operations. In such embodiments,
syringe drive 684 is advantageously piggybacked on z-positioner 206
such that syringe drive 684 moves with syringe 210 on z-axis
movements. This arrangement is illustrated in FIG. 6 (see
attachment of s-stepper motor 686 to frame 578).
[0068] It should be understood that, in the illustrated embodiment,
syringe drive 684 does NOT change the position of working syringe
210. Rather, syringe drive 684 changes the position of plunger 211.
Syringe drive 684 therefore causes a relative motion RM between the
body of the syringe 210 and plunger 211. Upward movement of plunger
211 thus generates a suction flow that causes any liquid in contact
with the tip of working syringe 210 to be aspirated therein.
Downward movement of plunger 211 generates a positive pressure that
forces any liquid that is within working syringe 210 to be
dispensed therefrom. And, as previously noted, in embodiments in
which syringe drive 684 is piggybacked on z-positioner 206 and
therefore moves along with working syringe 210, the z-positioner is
not operative to cause a relative motion between plunger 211 and
working syringe 210. In other words, z-positioner 206 does not
generate any aspirating or dispensing action in working syringe
210.
[0069] In embodiments in which working syringe 210 is integrated
into wash system 208, any movement of plunger 211 relative to the
body of working syringe 210 during liquid transfer operations will
affect flow conditions in wash system components. Those effects
will be described later in this Specification.
[0070] FIG. 7 depicts an illustrative embodiment of wash system 208
in accordance with the present teachings. For clarity of
illustration, syringe drive 684 is not shown in FIG. 7. For
reference, syringe drive 684 engages coupling member 694 (as
illustrated in FIG. 6). For further perspective, see FIG. 3,
wherein wash system 208 is depicted in conjunction with other
elements of illustrative SCR 200.
[0071] Illustrative wash system 208 includes two syringes in
addition to working syringe 210. The additional syringes include
wash syringe 702 having plunger 703 and waste syringe 704 having
plunger 705. Wash syringe 702 supplies cleaning fluid to working
syringe 210, while waste syringe 704 provides a suction flow that
removes contaminated cleaning fluid from well 707 in wash/waste
station 706 after it is has been used to wash working syringe
210.
[0072] Illustrative wash system 208 also includes supply reservoir
708 and waste reservoir 710. Supply reservoir 708 supplies cleaning
fluid to wash syringe 702, and waste reservoir 710 receives the
contaminated cleaning fluid that waste syringe 704 has aspirated
from well 707. The supply reservoir and the waste reservoir may
suitably be realized as standard flasks.
[0073] Various conduits place the various syringes in fluid
communication with supply reservoir 708, waste reservoir 710 and
wash/waste station 706. Wash/waste station 706 is made out of a
material that is selected for chemical compatibility with the
cleaning fluid and various reagents. Polyethylene has been found to
be an acceptable material for most applications.
[0074] In accordance with the present teachings, plunger 211 of
working syringe 210 and plunger 705 of waste syringe 704 cooperate
mechanically with coupling member 694 such that those two syringes
aspirate together and dispense together. On the other hand, wash
syringe 702 and its plunger 703 are configured such that wash
syringe 702 aspirates while the waste and working syringe dispense,
and wash syringe 702 dispenses while the waste and working syringe
aspirate. In accordance with some embodiments of the present
invention, plungers 211, 705 and 703 are all moved by the same
actuating device (i.e., syringe drive 684) at the same time.
[0075] The operation of wash station 208 is now described with
reference to the flow of cleaning fluid through the wash system as
a function of syringe drive movements, as depicted in FIGS. 7 and
8A-8C.
[0076] FIG. 8A depicts the "state" of the three syringes, and their
associated plungers, at the beginning of the previous operation
(i.e., before the wash cycle) wherein working syringe 210 is about
to dispense reagent into destination plate 260. As depicted in FIG.
8A, as plunger 211 is moved downwardly (via the action of syringe
drive 684) so that working syringe 210 can dispense reagent into a
well in a destination plate, plunger 703 is moved upwardly (via the
same movement of syringe drive 684).
[0077] As plunger 703 moves upwardly creating a suction flow, check
valve 714 opens and check valve 718 closes due to the one-way
nature of such check valves. With check valve 714 open, cleaning
fluid is aspirated from supply reservoir 708 through reservoir
supply conduit 712 and through wash syringe conduit 716 into wash
syringe 702. The check valves, which should have a low cracking
pressure (1.5 psi has been found to be acceptable), are available
from Upchurch Scientific of Oakharbor, Wash. All conduit used in
wash system 208 should be selected for chemical compatibility with
the chemicals being used. Teflon is suitable for many
applications.
[0078] As plunger 211 of working syringe 210 is forced downwardly,
plunger 705 of waste syringe 704 is also forced downwardly. As this
occurs, any used cleaner that had been drawn into waste syringe 704
(see description accompanying FIG. 8B) is dispensed, closing check
valve 724 and opening check valve 726. With check valve 726 open,
used cleaning fluid is forced through waste reservoir conduit 728
into waste reservoir 710.
[0079] Note the efficiency provided by (1) the integration of
working syringe 210 into wash station 208; and (2) driving both
working syringe 210 and wash system 208 with syringe drive 684. In
particular, wash system 208 is advantageously readying for the next
wash cycle during normal liquid transfer operations and is actuated
by the same drive that is dispensing working syringe 210 during
normal liquid transfer operations.
[0080] FIGS. 7 and 8B depict the state of the three syringes and
their plungers after reagent has been dispensed from working
syringe 210 into destination plate 260. In FIG. 7, wash/waste
station 706 has been positioned under working syringe 210 via x-y
positioner 201, and z-positioner 206 has dropped working syringe
210 into working syringe supply conduit 720. Working syringe 210 is
therefore ready to aspirate cleaning fluid.
[0081] As plunger 703 is moved into wash syringe 702 (via the
action of syringe drive 684), cleaning fluid is dispensed
therefrom. Due to the flow of cleaning fluid out of wash syringe
702 and through wash syringe conduit 716, check valve 714 closes
and check valve 718 opens. With check valve 718 open, cleaning
fluid flows into working syringe supply conduit 720. As plunger 703
moves into wash syringe 702, plunger 211 moves upwardly out of
working syringe 210. This upward movement creates a suction flow
that aspirates cleaning fluid into working syringe 210. Also, as a
consequence of its position partially within working syringe supply
conduit 720, the exterior of the needle or tip of working syringe
210 is washed with cleaning fluid.
[0082] Waste syringe 704 aspirates with working syringe 210. The
upward movement of plunger 705 creates a suction flow that opens
check valve 724 and closes check valve 726. Contaminated cleaning
fluid in well 707 is drawn into waste supply return conduit 722,
through check valve 724 and into waste syringe 704.
[0083] FIG. 8C depicts the state of the three syringes and their
plungers after cleaning fluid is dispensed from wash syringe 702
and aspirated by working syringe 210. During the next operation,
contaminated cleaning fluid is dispensed from working syringe 210.
In preparation for this operation, z-positioner 206 raises working
syringe 210 out of working syringe supply conduit 720.
[0084] As plunger 211 is moved downwardly into working syringe 210
(via the action of syringe drive 684), contaminated cleaning fluid
is dispensed from the working syringe into well 707. Moreover,
waste syringe 704 dispenses its load of contaminated cleaning fluid
(see description accompanying FIG. 8B) through check valve 726 and
waste reservoir conduit 728 into waste reservoir 710. At the same
time, wash syringe 702 aspirates fresh cleaning fluid in the manner
previously described (see description accompanying FIG. 8A).
[0085] After contaminated cleaning fluid is dispensed from working
syringe 210, the next reformatting cycle is ready to begin. And, as
the next reformatting cycle begins with working syringe 210
aspirating liquid from a source well, wash syringe 702 dispenses
fresh cleaning fluid to working syringe supply conduit 720 thereby
forcing any contaminated cleaning fluid in conduit 720 into well
707. Meanwhile, waste syringe 704 aspirates the contaminated
cleaning fluid from well 707. As previously noted, integrating
working syringe 210 into wash system 208, and using a single drive
to "power" both working syringe 210 and wash system 208 provides an
extraordinary level of efficiency to the washing operation, in
accordance with the present teachings.
[0086] The foregoing specific embodiment is generalized by the
following description of wash system 208. In accordance with the
present teachings, wash system 208 includes:
[0087] a first conduit (conduits 712 and 720) that is in fluid
communication with a supply of cleaning fluid (supply reservoir
708) and wash/waste station 706;
[0088] a second conduit (conduits 722 and 728) that is in fluid
communication with wash/waste station 706 and waste reservoir 710;
and
[0089] a fluid flow controller (syringe drive 684 in conjunction
with the plungers/syringes and conduit 716) for:
[0090] generating a flow of cleaning fluid from supply reservoir
708 to said wash/waste station 706, and
[0091] generating a flow of contaminated cleaning fluid from said
wash/waste station 706 to said waste reservoir 710.
[0092] To ensure proper flow of cleaning fluid through wash system
208, which is a closed system, waste syringe 704 should have a
greater capacity than wash syringe 702 and the wash syringe has a
greater capacity than working syringe 210. By way of example,
capacities of 590, 250 and 100 microliters for waste syringe 704,
wash syringe 702 and working syringe 210, respectively, have been
found to be suitable for use in wash system 208. The syringes
should be high quality, glass syringes such as Hydra syringes,
available from Robbins Scientific Corporation of Sunnyvale,
Calif.
[0093] FIG. 9 depicts method 900 for controlling SCR 200. Method
900 is advantageously implemented via processing and control
electronics 214, an illustrative embodiment of which is depicted in
FIG. 10.
[0094] In the illustrative embodiment depicted in FIG. 10,
processing and control electronics 214 includes processor 1042
running interactive SCR control software 1046. The SCR control
software, including updateable data file 1048, is stored in
memory/computer storage device 1044.
[0095] In accordance with operation 930 of illustrative method 900,
one or more "source-to-destination links" (hereinafter "links" or
"link data") that define the reformatting operations are specified.
Each such link specifies a well in a source plate from which liquid
is to be aspirated, and further specifies a well in a destination
plate into which the aspirated liquid is to be dispensed. There
are, of course, many ways in which operation 930 can be implemented
via interactive software, including a variety of user interface
options and, also, a variety of different data structures for
organizing the link data for use by the software. FIGS. 11-13
depict an illustrative embodiment of a graphical user interface
("GUI") 1100 by which link data and other operating parameters are
specified, and FIG. 14 depicts an illustrative embodiment of an
array 1454 of data structures 1456; for organizing the link data
within interactive software 1046.
[0096] Referring now to FIG. 11, in illustrative GUI 1100, source
plate (e.g., source plate 250 of FIG. 2) is selected via icon 1102.
"Clicking" on icon 1102 allows a user to select any of several
format options (e.g., 96-well plate, 384 well plate, 1536 well
plate, etc.). An alphanumeric description of the selected format
appears in selection box 1104. Moreover, graphical representation
1106 of the selected format advantageously appears in GUI 1100.
Graphical representation 1106 depicts a graphical representation
1108 of the appropriate number of wells for the selected
format.
[0097] The format of the destination plate (e.g., destination plate
260 of FIG. 2) is selected via icon 1112. A description of the
selected format appears in selection box 1114. Graphical
representation 1116 of the destination plate, including a graphical
representation 1118 of the appropriate number of wells for the
selected format, advantageously appears in GUI 1100.
[0098] In some embodiments, to specify a source well, a user simply
"clicks" on graphical representation 1108 of a well in the source
plate. Similarly, to select a corresponding destination well, the
user clicks on graphical representation 1118 of that well in the
destination plate. The selected wells are advantageously
"highlighted," and row-column descriptions 1110 and 1120 that
identify the selected wells advantageously accompanies the
graphical representations.
[0099] In other embodiments, the source and destination wells can
be selected by specifying a row number and a column number in
respective row-column descriptions 1110 and 1120. In such
embodiments, the graphical representations 1108 and 1118 of the
specified wells are advantageously highlighted to provide a
pictorial description. In yet additional embodiments, the wells can
be specified in both of the above-described ways.
[0100] Furthermore, rather than specifying new links in operation
930, SCR control software 1046 and GUI 1100 advantageously allow a
user to recall a previously specified group of links that have been
stored in memory 1044.
[0101] In some embodiments, graphical representations 1106 and 1116
of the plates keep track of selected links. In particular, in the
embodiment depicted in FIG. 12, the current source well selection,
which is located in the first row and second column, is highlighted
by first color R (e.g., red, etc.), while previously selected
source wells are highlighted in second color O (e.g., orange,
etc.).
[0102] One or more destination wells may be specified for each
source well. The destination wells being selected for the currently
selected source well are highlighted in first color R to depict the
correspondence between each destination well and the source well.
Destination wells that link to previously selected source wells are
highlighted by second color O. See FIG. 12. A user continues
specifying links using GUI 1100 until all intended links are
specified.
[0103] Link data for previously selected wells is advantageously
accessed through GUI 1100. For example, in one embodiment, such
data is accessed by "clicking" on a previously selected source
well. As depicted in FIG. 13, accessing the previously selected
source well in row 2, column 1 changes that well's highlighting
from second color O to first color R. All destination wells that
receive fluid from the source well are also displayed in first
color R.
[0104] Returning to method 900 depicted in FIG. 9, in optional
operation 932, syringe control parameters are specified, and in
optional operation 934, wash system parameters are specified.
Operations 932 and 934 are considered to be optional because SCR
200 could be operated with fixed values for these parameters. It
is, however, advantageous to allow a user to specify such
parameters.
[0105] In the embodiment depicted in FIG. 11, GUI 1100 is
configured to accept syringe control parameters. The syringe
control parameters included in GUI 1100 of FIG. 11 include the
volume of liquid dispensed from working syringe 210 and dispense
position corrections 1124. In the illustrated embodiment, syringe
dispense volume is specified by inserting a number, which does not
have to be an integer, in box 1122.
[0106] Regarding position corrections 1124, a user can specify the
radial position of the tip of working syringe 210 within a well,
wherein 0% correction corresponds to the center of the well and
100% correction corresponds to the wall or perimeter of the well.
This "horizontal" position correction allows a user to create
"touch-off" wherein a liquid droplet that forms at the tip of
working syringe 210 contacts the wall of the well. Touch-off
overcomes surface tension forces that tend to keep the droplet from
disengaging from the syringe. The horizontal touch-off correction
is specified by moving slider 1126 along the scale, as appropriate.
The specified touch-off correction appears in box 1128.
[0107] The "vertical offset" correction specifies how deeply the
syringe is positioned in a well, wherein 0% correction corresponds
to the bottom of the well and 100% correction corresponds to the
top of the well. This feature is particularly useful if, for
example, there is another liquid already in the well, since
contamination issues may arise if the syringe contacts that liquid.
The vertical offset correction is specified by moving slider 1130
along the scale, as appropriate. The specified vertical offset
correction appears in box 1132.
[0108] GUI 1100 of FIG. 11 is also configured to accept a wash
system parameter. In particular, the user may specify the number of
wash cycles that wash system 208 performs between reformatting
cycles. Wash cycles are specified via icon 1134. The selected
number of cycl'es appears in selection box 1136.
[0109] Returning to method 900 of FIG. 9, in operation 936, a
preferred execution order is determined for the links that were
specified in operation 930. Executing the links in the preferred
order will reduce overall reformatting time relative to the time it
would take to execute all such links in a random sequence. In one
embodiment of a preferred execution order, links are sequenced such
that:
[0110] (1) the destination well of each subsequent link is the
closest well to the destination well of the previous link; and
[0111] (2) irrespective of item (1), links sourced from the same
source well are executed before executing a link that draws from a
different source well.
[0112] For example, assume the following group of links is
specified:
1 Source Well Destination Well (row, column) (row, column) (2, 1)
(10, 15) (2, 1) (20, 30) (2, 1) (12, 25) (7, 6) (10, 16)
[0113] In accordance with the algorithm described above, these
links would be sequenced from first to last as follows:
[0114] [(2,1) (10,15)] [(2,1) (12,25)] [(2,1) (20,30)] [(7,6)
(10,16)].
[0115] It is within the capabilities of those skilled in the art to
develop an algorithm that sequences links as described above.
Moreover, it will be appreciated that other approaches for
sequencing links that will likewise reduce overall execution time
relative to a random execution sequence, as will occur to those
skilled in the art in view of the present teachings, may suitably
be used.
[0116] In the example described above, SCR control software 1046
operates such that even though more than one destination well may
be receiving liquid from a single source well (assuming the
transfer is to a denser format), the liquid transfer vehicle (e.g.,
syringe 210) returns to the source well for each transfer. In other
words, even though a sufficient volume of liquid could be aspirated
from the source well (e.g., source well (2,1)) to supply a
multiplicity of destination wells (e.g., (10,15), (12,25), and
(20,30)), a volume of liquid sufficient to supply only a single
destination well is withdrawn, per aspiration, from the source
well. In other embodiments, SCR control software 1046 is operative
to withdraw a sufficient volume of liquid from a source well to
supply multiple destination wells, as dictated by the specified
links. Using such an approach in conjunction with item (1) of the
sequencing algorithm further reduces reformatting time.
[0117] In operation 938, the specified links are executed.
Operation 938 can be initiated using GUI 1100 by "clicking" "start"
icon 1140. Start icon 1140 is advantageously grouped in control
panel 1138 with a palette of other icons that are operable to
initiate various functions. In the illustrated embodiment, control
1138 includes, in addition to start icon 1140, "pause" icon 1142,
"e-stop" icon 1144, "new" icon 1146, "open" icon 1148, "save" icon
1150 and "exit" icon 1152. Pause icon 1142 pauses the reformatting
operation at any point. E-stop icon 1144 is an emergency stop that
ends the reformatting run. New icon 1146 clears source and
destination plate links and allows a user to specify new links.
Open icon 1148 opens a saved file of links and save icon 1150 saves
a series of links. Exit icon 1152 exits the software.
[0118] In one embodiment, "execution" operation 938 includes
operations 940 through 944. In operation 940, spatial coordinates
for source and destination wells of links are obtained. In some
embodiments, such information is contained in updateable data file
1048 (see FIG. 10). In one embodiment, the information contained in
updateable data file 1048 includes, for each plate format:
[0119] (1) the absolute position of one well (typically well 1,1)
with the plate disposed in the source plate receiver 456 (see FIG.
3);
[0120] (2) the absolute position of one well (typically well 1,1)
with the plate disposed in the destination plate receiver 462 (see
FIG. 3); and
[0121] (3) the center-to-center well spacing for each format.
[0122] From this information, the spatial position of any well in a
plate, with the plate in either the source position or the
destination position, can be calculated in well known fashion. In
another embodiment, the x-y-z coordinates of each well are stored
in updateable data file 1048.
[0123] In operation 942, the spatial coordinates and other SCR
control parameters (e.g., syringe control parameters and wash
system control parameters, etc.) are transferred to controller
1050. Controller 1050 converts the spatial coordinates into
actuator control information that drives, in operation 944, x-y
positioner 201, z-positioner 206 and syringe drive 212 to aspirate
liquid from the specified source wells and dispense the aspirated
liquid into the specified destination wells. In terms of
illustrative SCR 200 depicted in FIG. 3, the actuator control
information is motor control information that drives, as
appropriate, s-stepper motor 686, z-stepper motor 570, y-stepper
motor 440 and x-stepper motor 1060 (not depicted in FIG. 3, see
FIG. 10).
[0124] Those skilled in the art will recognize that a stepper motor
driver operable to receive the motor control information from
controller 1050 is required in conjunction with each stepper motor.
The controller, which may be, for example, a 4-axis PC Card, is
available from Acroloop Motion Control Systems of Chaska, Minn.,
and the stepper motor drivers are available from Applied Motion
Products of Watsonville, Calif.
[0125] As will be appreciated by those skilled in the art, the
various positioning systems described herein advantageously include
a "home sensor" that provides a position reference to controller
1050. As depicted in FIG. 10, information from x-home sensor 1070,
y-home sensor 1072, z-home sensor 1074 and s-home sensor 1076 is
transmitted, via controller 1050, to processor 1042. It is within
the capabilities of those skilled in the art to suitably select a
home sensor and integrate it for use with any of the positioners
and/or drives mentioned herein. A suitable home sensor is available
from Omron of Schaumberg, Ill.
[0126] It will be appreciated that the functionality described
above may be implemented in software in many different ways by
those skilled in the art. For example, appreciable variation in the
order in which various tasks/operations are accomplished can be
expected, since the order of the operations comprising method 900
is substantially permutable. Moreover, a variety of different data
structures can be developed for organizing the link data. An
embodiment of one such data structure that provides certain
efficiencies in terms of computer resources and processing time is
described below in conjunction with FIG. 14.
[0127] To cover all possible links between wells on source plates
and wells on destination plates would require an array having a
maximum size of 1536.times.1536 (assuming a maximum plate density
of 1536 wells). Thus, an array having 2.4 million data structures,
each data structure containing the link data for a single link,
would be required. The present inventors have substantially reduced
the theoretical array size by recognizing that, notwithstanding the
2.4 million possible combinations, each well on the destination
plate can link with only one well on the source plate. In other
words, the link array can be reduced to a maximum of 1536 data
structures, one data structure for each well on the destination
plate. Such an array of data structures is depicted in FIG. 14.
[0128] Link array 1454 contains a number N of data structures
1456.sub.i, where N is the number of wells in the destination
plate. Each data structure 1456.sub.i contains row and column
designation 1458 of a source well and row and column designation
1460 of a destination well. In some embodiments, each data
structure 1456.sub.i includes link status 1462 for indicating
whether the link is active (ie., liquid is being dispensed to that
particular destination well) or not, and whether the link has been
executed if it is active. Additionally, in some embodiments, each
data structure 1456.sub.i contains an execution priority 1464 as
determined in operation 936 of method 900 (see FIG. 9).
[0129] It is to be understood that the above-described embodiments
are merely illustrative of the invention and that many variations
can be devised by those skilled in the art without departing from
the scope of the invention. It is therefore intended that such
variations be included within the scope of the following claims and
their equivalents.
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