GB2452628A

GB2452628A - Liquid delivery apparatus

Info

Publication number: GB2452628A
Application number: GB0816273A
Authority: GB
Inventors: Arne Deggerdale
Original assignee: Mole Genetics AS
Current assignee: Mole Genetics AS
Priority date: 2007-09-07
Filing date: 2008-09-05
Publication date: 2009-03-11
Anticipated expiration: 2028-09-05
Also published as: GB0816273D0; GB0717451D0; GB2452628B

Abstract

A work surface assembly for use in an automated liquid handling device is provided wherein the pipette assembly moves only in the horizontal axis. The work surface is arranged (or the modules are ordered) so as to minimise contamination when the pipette is passing over used wells or liquids used later in the process. This is done by providing the following elements on the work surface B1: pipette tip holder C, output container holder D, waste container holder B3, reaction container holder B4, and a central reagent container holder A. The elements are arranged in that order from the periphery to the centre of the work surface, the same elements are then arranged in an inverted repeat in the remainder of the work surface. The central (common) reagent container holder may be thermostatically or temperature controlled such as by a Peltier block. An automated liquid handling device comprising such a work surface assembly, and a method for processing a plurality of samples therein are also claimed.

Description

LIQUID DELIVERY APPARATUS

The present invention relates to a work surface assembly for use in an automated liquid handling device, an automated liquid handling device comprising such a work surface assembly, and a method for processing a plurality of samples therein.

Automated liquid handling devices are commonly used in laboratories. In molecular biology, for example, nucleic acid separation processes may be operated in an automated device often using magnetic particles as a means to separate the nucleic acid from contaminating material. Devices are commercially available which may include an automated pipette head assembly movable within the device so that it may be aligned with test tubes or vials for reagent liquid handling. Apparatus of this type has been made to very high standards of engineering, using high quality durable machinery which may be precision manufactured to ensure that operation of the device is reliable. Usually, devices of this type include a dedicated microcomputer to enable programmable control of the processes which the device must perform. Such devices are generally expensive to purchase and may require specialist service contracts for maintenance.

J.n a typical automated liquid handling device a pipette head assembly uses disposable pipette tips to aspirate and release samples and reagents. Aspiration and release may be performed according to protocols operated by programming the dedicated microcomputer. A work surface assembly is provided which comprises various elements to enable positioning of pipette tips, reagent containers, sample containers and the like. A multi-well format is frequently adopted so that a number of parallel pipetting channels can be employed simultaneously to enable simultaneous processing of a number of samples.

When the automated liquid handling device processes samples, for example so as to purif' a molecule from a complex mixture, there are two primary concerns that govern the layout of the work surface. Firstly, there should be no contamination between wells containing one sample and wells containing another sample. This is commonly referred to as cross-contamination. Secondly, there should be no contamination from early stages of a purification of a sample into unused liquids that will be used at a later stage of the purification of the same sample. Instruments have therefore been designed with movement of the pipette assembly along only one horizontal axis. In this way, n parallel pipetting channels may be employed side by side so as to treat n samples at a time without risk of drops falling from the pipette tips into wells being used for purification of another sample. It is also known to take care to design the system so that used pipette tips only pass over used wells, tips and tubes.

In this way, it is also possible to avoid the risk of drops falling from the pipette tips into unused liquids that will be used at a later stage of the purification of the same sample.

There is often a need to process a maximum number of samples in an automated liquid handling device without re-loading the device. There are two known ways of processing 2n samples without increasing the risk of contamination. These are illustrated in Figures 2 and 3 which are discussed in fUrther detail below. According to the arrangement of Figure 2, it is not possible to avoid the risk of contamination unless a mechanical device is added which will sit under the pipette tips while they are moving and swing away when pipetting is performed. In a device like this, it would normally be possible to catch any drops that fall from the pipette tip. However, a disadvantage of these devices is that they are expensive to produce and also require maintenance. Figure 3 shows a second way to avoid contamination. Here, a tandem set of work surfaces is provided. Because all parts of the work surface must be duplicated, the production cost is significantly increased.

The present invention addresses the problem of processing multiple samples in an automated liquid handling device without re- loading and without increasing the risk of contamination.

In a first aspect, the present invention provides a work surface assembly for mounting in an automated liquid handling device, which comprises the following elements arranged adjacent to each other along a horizontal axis in the sequence: a first pipette tip holder; a first output container holder; a first waste container position; a first reaction container holder; a reagent container holder; a second reaction container holder; a second waste container position; a second output container holder; and a second pipette tip holder, wherein the output and reaction container holders each hold no more than one container along the horizontal axis.

The present invention avoids the need to duplicate all components of the work surface assembly by providing an arrangement of elements in an inverted repeat rather than in

a tandem repeat according to the prior art.

The first "half' of the work surface assembly comprises the first pipette tip holder, first output container holder, first waste container position, first reaction container holder and a first half of the reagent container holder in a direction along the horizontal axis of the device. The second "half' is made up of the remaining elements which typically provide a mirror image of the first half. By arranging the elements adjacent to each other along the horizontal axis no additional pipette tip holders, containers or other apparatus for liquid processing are positioned between each of the elements of the work surface assembly. This enables processing of samples to be set up so that contamination risk is avoided.

This arrangement of elements is particularly advantageous because the reagent container holder is generally an expensive component requiring, for example, a heater/cooler or a mechanical handling device. The reagent container holder is an element common to the two halves of the arrangement of elements and does not need to be duplicated. This reduces the cost of production of the assembly and device and avoids the risk of contamination.

Typically, each tip or container holder is arranged to hold a plurality of tips or containers so as to provide a plurality of parallel channels along the horizontal axis.

For example, each container holder may define a row of locations in a horizontal direction perpendicular to the horizontal axis of the work surface of an assembly. The output and reaction container holders may thus comprise a single row of, for example, 8 positions for output and reaction containers. The reagent container holder may comprise a plurality of rows, for example in an 8x 12 arrangement or similar multi-well arrangement. This enables a plurality of different reagents to be arranged in the reagent container holder for use in processing the samples.

The reagent container holder may comprise a square well block. The reagent container holder may comprise a temperature-controlled holder such as a Peltier block or other thermostatically controlled block, depending on the treatment of the sample required. Other heaters, coolers and shakers known in the art may be used with the reagent container holder.

The present invention further provides an automated liquid handling device which comprises a work surface assembly as described herein. The device may further comprise a pipette head assembly mounted for movement along the horizontal axis of the work surface assembly. In operation, the pipette head assembly may be operated according to a protocol which confines its movement to first one half, then the other half of the work surface assembly.

Accordingly, the invention further provides a method for processing a plurality of samples in an automated liquid handling device. The method comprises processing a first sample or series of samples by confining movement of the pipette head assembly to positions along the horizontal axis from the first pipette tip holder up to halfway along the reagent container holder; and processing a second sample or series of samples by confining movement of the pipette head assembly to positions along the horizontal axis from the second pipette tip holder up to halfway along the reagent container holder; whereby no used pipette tip passes over an unused container.

The present invention will now be described in further detail by way of example only, with reference to the accompanying drawings, in which: Figure 1 shows a work surface assembly according to the present invention; Figure 2 shows a work surface assembly according to the prior art; Figure 3 shows a work surface assembly according to the prior art; and Figure 4 shows an automated liquid deLivery apparatus according to the present invention.

Figure 4 shows the principal features of a liquid delivery apparatus according to a specific embodiment of the invention. Instrument frame 0 generally forms part of a cabinet for laboratory bench top use. Work surface assembly F is made of stainless steel and provides a surface for mounting or positioning various other elements of the apparatus. Pipette storage plate G enables storage of pipette tips. A holder for elution tubes I is provided adjacent the pipette tip storage plate. A waste box position H enables waste to be disposably located therein. Positions for sample tubes K are provided adjacent the waste box position. Peltier block P is provided on the work surface assembly F and incorporates a sequence well block for containing reagents.

Further positions for sample tubes K, holder for elution tubes I and pipette tip storage plate 0 are also provided at the opposite side of the Peltier block P. Pipette head assembly P is movable horizontally and vertically. Horizontal movement is achieved by attachment of the assembly to rails along the back wall of the apparatus frame and the assembly is driven by a drive belt powered by a motor (not shown).

Vertical movement is achieved by mounting the head on a threaded axle which is driven by a further motor. A pipette tip ejector is provided on the pipette head and the head is shown in the Figure with a single disposable pipette tip. The pipette head may attach a plurality of disposable pipette tips.

The magnetic rod E4 comprises a standard aluminium rod to which are secured magnets E5. The magnets are seated in holes in the aluminium rod and are attached to a flat steel rod (not shown) which sits in a groove in the aluminium rod. Module carriage E6 provides a mounting for magnetic rod E4 and motor El. At the end of the magnetic rod proximal to the module carriage E6 is provided a small carriage part slidably mounted on vertical rail E7. Motor El drives threaded axle E2, which passes through nut E3 fixed to the small carriage part of the magnetic rod to provide vertical movement on the vertical rail E7. Module carriage E6 is mounted for horizontal movement along the horizontal rail to enable the entire assembly including magnetic rod E4 and motor El to move horizontally. Drive belt J turns over a free pulley N on one side and over a pulley fixed to the axle of the motor on the other side (not shown) to provide horizontal movement along the rail.

Figure 1 shows a specific embodiment of a work surface assembly according to the invention. Bi shows generally the stainless steel work surface which is supported by work surface support B2. B3 shows a hole for a waste container and holes B4 are for sample tubes or reaction tubes. Next to the hole for the waste container B3 is situated an output tube holder D. Adjacent to the output tube holder is pipette tip holder C. Each of these elements is mirrored on the left and right hand side of the assembly as shown in the figure. Peltier-based cooler/heater A is situated centrally for controlling the temperature of reagents sitting in wells of a square-well block. The Peltier-based cooler/heater is shared by both halves of the work surface assembly. Up to 6 rows of square wells on the left hand side of the square-well block may be used in conjunction with the elements on the left hand side of the work surface assembly. The corresponding 6 wells on the right hand side of the block are used in conjunction with the corresponding elements on the right hand side of the assembly.

In operation, the work flow with reference to Figure 1 is as follows. Clean tips are picked up from the pipette tip holder C and moved to the left-most square wells in A to pick up the first reagent to be used. A clean tip is no contamination hazard. The first liquid is moved to the sample/reaction tube in position at B4, not passing over any other well on the way. With the same tip, reagent number 2 is picked up from the next column of square wells, only passing over the now empty well. In a similar way, each time a new reagent is picked up, a pipette will pass over only those wells that are either empty or containing liquid that is a waste product from a previous step. When used tips are discarded in the waste container B3, the tip does not pass over anything between the sample/reaction tube and the waste container. The output tubes positioned at D are only passed over by clean tips until the finished product is placed there. When the first 8 samples have been processed, the processing of the next 8 samples can commence with picking up a clean tip and aspirating the first reagent from the right-most square well. The process then proceeds as a mirror image of the process of the first 8 samples. In other words, the process operates as an inverted repeat.

Figure 2 shows one prior art arrangement of performing the same task without using a repeat of the work surface. With an arrangement like this, it is impossible to avoid passing over clean positions with a tip containing liquid. Two rows of output tube holders are situated at D and two rows of holes for sample tubes/reaction tubes are situated at B4. Additionally, the number of pipette tips held by the pipette tip holder are doubled. In order to achieve a level of protection against contamination, additional mechanical parts configured to catch accidental spills or drops must be designed and installed with this conventional work surface assembly.

Figure 3 demonstrates how a direct repeat of a work surface assembly can be used to accomplish the task with a good level of protection against contamination. However, two independent Peltier-based coolerfheater elements are required to achieve a direct repeat.

Claims

Claims: 1. A work surface assembly for mounting in an automated liquid handling device, which comprises the following elements arranged adjacent to each other along a horizontal axis in the sequence: a first pipette tip holder; a first output container holder; a first waste container position; a first reaction container holder; a reagent container holder; a second reaction container holder; a second waste container position; a second output container holder; and a second pipette tip holder, wherein the output and reaction container holders each hold no more than one container along the horizontal axis.
2. A work surface assembly according to claim I, wherein each tip or container holder is arranged to hold a plurality of tips or containers so as to provide a plurality of parallel channels along the horizontal axis.
3. A work surface assembly according to claim I or claim 2, wherein the reagent container holder comprises a temperature-controlled holder.
4. A work surface assembly according to claim 3, wherein the temperature-controlled holder comprises a Peltier block.
5. A work surface assembly according to claim 3 or claim 4, wherein the reagent container holder comprises a square well block.
6. An automated liquid handling device which comprises a work surface assembly according to any preceding claim.
7. An automated liquid handling device according to claim 6, which further comprises a pipette head assembly mounted for movement along the horizontal axis of the work surface assembly.
8. A method for processing a plurality of samples in an automated liquid handling device according to claim 7, which method comprises processing a first sample or series of samples by confining movement of the pipette head assembly to positions along the horizontal axis from the first pipette tip holder up to halfway along the reagent container holder; and processing a second sample or series of samples by confining movement of the pipette head assembly to positions along the horizontal axis from the second pipette tip holder upto halfway along the reagent container holder; whereby no used pipette tip passes over an unused container.