Background Art Many operations that require precise manipulation of a position within an X-Y array. use a tool to either travel along a defined X-Y track. or to move a table supporting the array underneath a fixed tool. The length of the track or the throw of the ball and screw defines the size of the array that can be manipulated. For many applications the size of the X-Y table is not a limiting factor but for some applications where space is at a premium or where a particularly large array or object has to be manipulated requiring a large X-Y table. there is a need to develop a device where a large array can be manipulated on a small X-Y table.

For some large arrays, belt drive systems can be used in place of ball and screw X-Y drives. However belt drive systems are less accurate than ball and screw drives, and are typically accurate to only 500 microns as opposed to the 100 micron accuracy possible with ball and screw drives. and are unsuitable for some applications. Even with belt drive systems, there is a limit to the size of the array which can be manipulated.

Often the array also has to be imaged, prior to manipulation or treatment of the array. For example in applications where samples have to be excised from an the array, it is necessary to image the array and transform the (x. y) coordinates of the samples within the array into robot (x, y) coordinates or into some other suitable coordinate system. One such application is removing samples from a large format electrophoresis array which is typically in the order of 18 to 25 cm in the x-axis and 18 to 25 cm in the y- axis. The quality of the image acquisition is a balance between focal length and the diameter and zoom of the lens. For instruments where the focal length is fixed, it is necessary to use a wide-angle setting to capture the entire array. This leads to a"pin-cushion"effect due to lens aberration. The wider the angle, the greater the"pin-cushion"and the greater the need to

compensate for coordinates on the perimeter of the image. This compensation required may be too great to achieve with 100% accuracy and hence may lead to an impractical instrument format where image coordinates do not properly correspond to robot coordinates.

The present inventors have now realised that it is possible to develop an improved apparatus suitable for the manipulation of a large surface area while minimising the distance the array-support table or manipulation tool is required to travel.

Summary of the Invention In a first aspect of the present invention there is provided an apparatus for manipulating an array on an X-Y platform comprising: (a) imaging means for recording an electronic image of the position of at least one portion of the area of the array; (b) means for utilising the recorded image so as to control or move a tool or the like relative to the array to manipulate or act on a part of the imaged area of the array in situ: (c) means for rotating the array by a predetermined angle so as to record an electronic image of the position of a second portion of the area of the array ; (d) control means for controlling means (a), (b), and (c), wherein means (b) acts on a part of the array according to the position of that part of the array relative to the rest of the array as determined by imaging means (a).

In a preferred embodiment means for rotating the array by a predetermined angle is a turntable.

Typically the predetermined angle will be 90 degrees so that a quarter of the array will be imaged at a time.

In a related aspect the invention provides a method of manipulating an array on an X-Y platform comprising the steps of:- (a) recording an electronic image of the position of at least one portion of the area of the array; (b) utilising the recorded image so as to control or move a tool or the like relative to the array to manipulate or act on a part of the imaged area of the array in situ; (c) rotating the array by a predetermined angle so as to record an electronic image of the position of a second portion of the area of the array ;

(d) repeating step (c) until the entire array has been imaged; The steps (a) to (c) may be repeated or cycled so as to carry out a series of manipulations of a number of different samples in the array.

The entire array may be imaged before step (b) is carried out i. e. steps (a), (c) and (d) are carried out for the entire array before step (b) is carried out, in which case after the array has been imaged, the array will be periodically rotated to make each imaged portion available to the tool.

One typical example of the need for a small X-Y table but a large surface area for manipulation is the requirement to carry out definitive analyses of biomolecules, such as, but not exclusively, proteins, peptides, polysaccharides, lipids, and nucleic acid molecules or complex molecules like glycoproteins. The biomolecules may have been separated by means of electrophoresis in a polymer matrix then placed or transferred to a solid support or membrane for example. For example, two dimensional electrophoresis separations in polyacrylamide or transferred to supports like PTFE. gortex. PVDF, nylon, nitrocellulose, polypropylene are particularly suitable to form the array. It is necessary to excise the biomolecule from the array and transfer them separately to a vessel such as a microtitre plate.

In order to manipulate the array with precision and keep it intact, the array is supported on a turntable. An electronic image of one section of the samples in the array (typically not less than one quarter) is acquired.

In a preferred embodiment of the present invention, the electronic image is generated from a digital photograph of the samples to allow them to be visualised and their coordinates recorded. These coordinates are then transformed into robotic language whereupon an excision tool can be directed to a selected sample or that the sample is moved below a fixed tool.

Preferably the section which is imaged is closest to the tool so that the distance the tool is required to travel to manipulate the array is minimised. When all manipulations are complete the array is rotated 90°. A second section of the array is now imaged and manipulated. This process is repeated until at least one sample from the array has been manipulated.

The computer control means may process all captured images following rotation and assemble a complete image of the array that contains the information relevant to which samples within the array were manipulated. The position of all the samples would be known from their co- ordinates corresponding to the image acquired following rotation of the array.

Each sample manipulated from images other than the first would require transformation vectors to annotate their true x. y coordinates in the assembled array.

In order that the present invention may be more clearly understood, preferred forms will be described with reference to the following examples and accompanying drawings.

Brief Description of Drawings Figure la is a schematic side view of an apparatus for imaging and manipulating a sample embodying the present invention ; Figure 1b is a plan view of the apparatus of Figure la viewed from above illustrating a turntable which forms part of the apparatus; Figure 2a shows four separate recorded images of the array following sequential 90° rotations of the turntable; and Figure 2b shows a reassembled image of the entire array.

Detailed Description Of The Presently Preferred Embodiments Turning now to the drawings, Figure la shows an embodiment of an apparatus for imaging and manipulating a sample, also referred to as a sample excision robot and generally indicated at 100. The sample excision robot 100 includes a turntable 105. The sample excision robot 100 further comprises an image acquisition system 200. an excision tool 400, and a computer control means 300. The turntable 105 is housed inside an acrylic base plate 101 which may be illuminated from underneath the sample with fluorescent light (for acrylamide gels) or from above with tungsten lamps or the camera flash 106 (for membranes). An array of samples is placed onto the turntable. Typically, the array will be biomolecules separated by electrophoresis in polymer based array. The array of biomolecules is placed or transferred to a solid support or membrane and then placed on the turntable.

Only a subset of the array is imaged (typically not less than one quarter) and is transferred from the camera to the computer 300. The image is processed and imported into"click-on-a-spot"software. This process translates the image pixel coordinates into robot coordinates. The"click-on- a-spot"software is then used to drive the excision tool 400 to the selected component via an x. y movable bar 102. X-Y movement is generated by the

tool. The reverse would however be possible, with the table moving in X-Y directions and the tool being fixed in the X and Y directions but, of course movable in the Z axis for cutting and retrieving spots from the sample array.

Also both table and tool could move, if desired. The Z axis movement of the excision tool 400 is provided via an excision tool support unit 107. The excised sample is then deposited into a chosen well of a microtitre plate 108.

The turntable 105 is shown in plan view Figure 1b in which the sample excision robot 100 is viewed from above with the camera mount 106 removed for clarity. The turntable 105 may be made of a number of suitable materials including glass, metal or plastic. However, it is preferable if the table is translucent as this makes it possible to image acrylamide gels by underlighting. The area manipulated by the tool is highlighted in hatching 109. Hence. the remaining area of the sample table/array may be covered with a protective plate and used for other functions such as supporting replacement excision tool cutting heads and accessories and supporting additional microtitre plates As well as enabling the use of a smaller X-Y table the provision of the turntable means that the excision tool has less distance to travel than if it was working on the entire array. Typically the tool will travel only half the distance that it would have to travel if the turntable were not provided. This is particularly important where the tool moves back and forth from a location on the array to a different location but less important than in other operations such as an engraving operation where the tool would typically remain on the array during the engraving process and slowly move across the array.

Figure 2a shows a processed array. Each quadrant of the array is independently imaged following rotation of the turntable by 90°. The array is manipulated in the rotated positions (quad 1-quad 4). Following processing of the entire array, the 4 images are processed and assembled to prepare an image of the entire array as shown in Figure 2b.

The samples may be excised after each quadrant has been imaged or after the entire array has been imaged. If the samples were excised after the entire array has been imaged the computer control means would have to recognise whether the co-ordinates related to the quadrant of the array which was presently accessible by the cutting tool or whether the turntable would have to be rotated to access the relevant quadrant.

In an alternative embodiment instead of using a turntable, the array could be manually manipulated by sequentially rotating it by 90°, whether supported by a turntable or not. Following rotation the images are acquired.

The invention is not limited to use in excision tools and can be used in any application where a table has to move in X and Y directions for an operation to be carried out on an array or object supported on the table.

Clearly the turntable may be rotated by angles other than 90°.

It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the invention as shown in the specific embodiments without departing from the spirit or scope of the invention as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.