Single channel reformatter

Details Single channel reformatter Single channel reformatter

2000-04-24

2004-02-17

Picard, Leo (Department: 2125)

Data processing: generic control systems or specific application

Generic control system, apparatus or process

Digital positioning

C700S057000, C700S060000, C700S061000, C700S083000, C422S065000, C422S105000

Reexamination Certificate

active

06694197

ABSTRACT:

FIELD OF THE INVENTION
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
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.
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.”
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.
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.
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.
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
.
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.
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).
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
.
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
128
A 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
.
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).
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.
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.
A need therefore exists for an improved single channel reformatter.
SUMMARY OF THE INVENTION
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.
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.
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

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