Abstract: In one aspect the present invention provides a method for selecting a cell or cell colony which produces a polypeptide of interest, comprising a) providing a medium comprising cells and a detection agent, wherein the detection agent is associated with a detectable signal and the detection agent is capable of binding to the polypeptide of interest; b) providing a solid phase having a capture agent disposed thereon, wherein the capture agent is capable of binding to the polypeptide of interest; c) contacting the medium with the solid phase; d) detecting the signal associated with the detection agent; and e) selecting a cell or cell colony associated with the signal, wherein presence of the signal is indicative of a cell or cell colony which produces the polypeptide of interest.

Abstract: An apparatus and method for automated picking of animal cell colonies is described. A picking head comprising a plurality of hollow pins is provided. The apparatus has an integrated imager for capturing an image of adherent or non-adherent animal cell colonies held in liquid or semi-solid medium. Image processing identifies the locations of the animal cell colonies to be picked. Picking an animal cell colony is performed by aligning each of the hollow pins in turn with a target animal cell colony location, introducing the hollow pin into the medium, and aspirating the animal cell colony into the hollow pin. In the case of an adherent colony, the distal end of the pin is forced into oscillation to detach the animal cell colony prior to aspiration. The animal cell colony is dispensed into a well plate by increasing pressure in the fluid conduit.

Abstract: An apparatus and method for automated picking of animal cell colonies. A picking head comprising a plurality of hollow pins is provided. The apparatus has an integrated imager for capturing an image of adherent or non-adherent animal cell colonies held in liquid or semi-solid medium. Image processing identifies the locations of the animal cell colonies to be picked. Picking an animal cell colony is performed by aligning each of the hollow pins in turn with a target animal cell colony location, introducing the hollow pin into the medium, and aspirating the animal cell colony into the hollow pin. In the case of an adherent colony, the distal end of the pin is forced into oscillation to detach the animal cell colony prior to aspiration. The animal cell colony is dispensed into a well plate by increasing pressure in the fluid conduit.

Abstract: A calibration method for a flow cytometer with a multichannel detector module. During calibration, the fluorescence intensity data values for the different detector channels are used to calculate normalization factors needed to adjust subsequent data collected by each of the channels. By using a multichannel detector module, the results from the different flow cells can be reliably compared, so that multiple stages of flow cells can be arranged in series along a common flow path, for example to measure the same sample at defined time intervals.

Abstract: An apparatus and method for automated picking of animal cell colonies. A picking head comprising a plurality of hollow pins is provided. The apparatus has an integrated imager for capturing an image of adherent or non-adherent animal cell colonies held in liquid or semi-solid medium. Image processing identifies the locations of the animal cell colonies to be picked. Picking an animal cell colony is performed by aligning each of the hollow pins in turn with a target animal cell colony location, introducing the hollow pin into the medium, and aspirating the animal cell colony into the hollow pin. In the case of an adherent colony, the distal end of the pin is forced into oscillation to detach the animal cell colony prior to aspiration. The animal cell colony is dispensed into a well plate by increasing pressure in the fluid conduit.

Abstract: Disclosed herein is a holder for biological sample containers such as well plates. The holder comprises a flat vacuum bed surrounded by a seal. A container is placed within the seal and a vacuum is applied, pressing and flattening the lower surface of the sample container against the flat vacuum bed. Samples in all portions of the container may then be imaged without the need to refocus on each portion of the container. For imaging, a sample in a well can be illuminated by a beam of light arranged so that a part or all of the sample is illuminated by direct rays that have not passed through the well plate. The beam is redirected to other parts of the well if a single illumination does not cover the whole well, so that the sample to be imaged using a series of partial images.

Abstract: The present invention provides in one aspect a method for determining a production level of a polypeptide of interest by a cell or cell colony, comprising obtaining an image of one or more cells or cell colonies; and analyzing the image to detect a signal associated with the polypeptide of interest; wherein a signal level is determined for each cell or cell colony based on signal values from a predefined area surrounding the cell or cell colony, the signal level being indicative of the production level of the polypeptide of interest by the cell or cell colony.

Abstract: An apparatus and method for optically analyzing samples in a biological sample container containing samples arranged at different locations on the base of the container. An optical acquisition device is provided comprising a detector and an objective. The position of the upper and lower surfaces of the base at each of the sample locations is determined by a confocal polychromatic displacement sensor. Light is collected from each of the sample locations by adjusting the focal plane to be coincident with, or vertically offset from, the upper surface of the base, as determined from the displacement sensor. This allows for rapid scanning of large numbers of samples in a multi-well plate or other biological sample containers.

Abstract: A liquid handling robot for handling well plates. The robot has a powered anvil which loads pipette tips from a tray onto the cones of a liquid handling head by first clamping the liquid handling head to the anvil and then ramming a movable plate carrying the pipette tips onto the cones. The robot also allows for fully automated swapping between different heads, such as liquid handling heads or pin heads. A head parking station is provided for parking heads when they are not being used. The robot has an automated pipette tip tray dispenser based on storage cassettes that store vertically stacked pipette tip trays.

Abstract: An apparatus and method for optically analyzing samples in a biological sample container containing samples arranged at different locations on the base of the container. An optical acquisition device is provided comprising a detector and an objective. The position of the upper and lower surfaces of the base at each of the sample locations is determined by a confocal polychromatic displacement sensor. Light is collected from each of the sample locations by adjusting the focal plane to be coincident with, or vertically offset from, the upper surface of the base, as determined from the displacement sensor. This allows for rapid scanning of large numbers of samples in a multi-well plate or other biological sample containers.

Abstract: A robotic apparatus of the kind having a sample manipulation head with associated positioning system mounted above the main bed of the apparatus, as used for picking of cells, in particular animal cells, or for other biological or chemical applications. An imaging station is arranged on the main bed where a sample container containing a sample can be placed in an object position. According to the invention, both excitation and collection optical sub-systems are mounted under the main bed of the apparatus for performing spectroscopic analysis on a sample at the imaging station. The integration is based on a reflection mode optical solution, which allows all the optical components to be mounted under the main bed of the apparatus. Consequently, ancillary software driven or manual processes can be carried on with whether or not spectroscopic measurements are being made.

Abstract: A method of cleaning a pin head or other implements between handling a plurality of samples of nucleic acid subject to an amplification process using a biochemical amplification product. The method comprises exposing the pin head or other implement to ultraviolet (UV) and preferably also infrared (IR) illumination between handling different samples in order to suppress cross-contamination by non-specific amplification. The biochemical amplification product may be obtained from a rolling circle amplification (RCA) procedure, such as that catalyzed by bacteriophage phi29, or a polymerase chain reaction (PCR) amplification product.

Abstract: A high throughput microarraying or colony picking robot with an automatic mechanism for exchanging pin heads and an automated washing and drying apparatus. The robot allows a dirty pin head to be deposited on the automated washing and drying apparatus for cleaning without use of the xyz-positioner, while spotting or picking can continue by picking up a clean pin head without having to wait for the dirty pin head to be cleaned. In this way, the speed of operation can be increased without any increase in the acceleration or speed of the x-, y- and z-drives. The dead time normally associated with the washing and drying cycle, which is usually several minutes, is therefore eliminated, and replaced with the much shorter dead time, of only a few tens of seconds, needed for changing between heads.

Abstract: A liquid handling robot for handling well plates. The robot has a powered anvil which loads pipette tips from a tray onto the cones of a liquid handling head by first clamping the liquid handling head to the anvil and then ramming a movable plate carrying the pipette tips onto the cones. The robot also allows for fully automated swapping between different heads, such as liquid handling heads or pin heads. A head parking station is provided for parking heads when they are not being used. The robot has an automated pipette tip tray dispenser based on storage cassettes that store vertically stacked pipette tip trays.

Abstract: Apparatus for handling biological sample containers comprises a conveyor assembly for conveying containers and a lid handling assembly operable to remove lids from and replace lids onto containers while the containers are in motion on the conveyor assembly. The lid handling assembly comprises a pair of ramps onto which a lid is lifted by a lifting mechanism configured to handle overhanging lids or non-overhanging lids as required. The lid handling assembly may be configured to handle lids of containers of various sizes by altering the ramp spacing. A conveyor assembly comprises a pair of converging rails which carry a pair of jaws operable to carry a container. The convergence of the rails makes the jaws clamp the container so that it is held tightly in position for micro-arraying to be carried out. The conveyor assembly may be adapted to handle different sizes of container by the provision of holders to hold various container types.

Abstract: A multiwell plate for microarraying comprising a self-sealing lower membrane and optionally also a self-sealing upper membrane. Spotting is performed by pushing a pin down through the liquid and then on to pierce the self-sealing lower membrane. A slide having an upper spotting surface is arranged under the well plate. The liquid sample forced through the lower membrane by the pin tip can thus be deposited directly onto the spotting surface. The pin is then withdrawn upwards through the lower membrane, which automatically reseals preventing further loss of liquid. The optional resealable upper membrane also prevents loss of sample liquid by evaporation and spillage. By contrast to the prior art, there is the major advantage that the pin head does not have to traverse between the well plate and slide to collect sample liquid, thus dramatically increasing operational speed for an automated microarraying apparatus employing the multiwell plate. Excellent spot reproducibility is also observed.

Abstract: Apparatus for handling biological sample containers comprises a conveyor assembly for conveying containers and a lid handing assembly operable to remove lids from and replace lids onto containers while the containers are in motion on the conveyor assembly. The lid handling assembly comprises a pair of ramps onto which a lid is lifted by a lifting mechanism configured to handle overhanging lids or non-overhanging lids as required. The lid handling assembly may be configured to handle lids of containers of various sizes by altering the ramp spacing. A conveyor assembly comprises a pair of converging rails which carry a pair of jaws operable to carry a container. The convergence of the rails rakes the jaws clamp the container so that it is held tightly in position for micro-arraying to be cared out. The conveyor assembly may be adapted to handle different sizes of container by the provision of holders to hold various container types.

Abstract: A pin holder for a microarraying apparatus comprising at least one group of bodies of circular cross-section packed together to form a network of pathways in gaps between the bodies; and an array of pins slidably arranged in the pathways. The pins are held in parallel to each other automatically as a result of the self organized packing of the circular cross-section bodies, which may be spheres, for example ball bearings, or cylindrical, for example needle roller bearings. The pin holder provides for very accurate parallel alignment of the pins, low pin friction, as well as low cost and complexity of manufacture.

Abstract: The invention is based on the realization that feedback control for the vertical drive of a pin head becomes unnecessary if one instead prealigns the relative heights of the spotting surface and the well plates such that the pins in the pin head are lowered to the same absolute height both for picking up liquid from the well plates and depositing it onto the spotting surface. By aligning the heights of the well plates and spotting surfaces, the vertical drive of the pin head needs only to be able to reproducibly and accurately arrive at a single lowered position. A pin head can provide this functionality by having a mechanically defined bottom point, obviating the need for a complex and costly feedback control system for height determination of the pins. A simple, low-cost micro-arrayer can thus be provided.

Abstract: A high throughput microarraying or colony picking robot with an automatic mechanism for exchanging pin heads and an automated washing and drying apparatus. The robot allows a dirty pin head to be deposited on the automated washing and drying apparatus for cleaning without use of the xyz-positioner, while spotting or picking can continue by picking up a clean pin head without having to wait for the dirty pin head to be cleaned. In this way, the speed of operation can be increased without any increase in the acceleration or speed of the x-, y- and z-drives. The dead time normally associated with the washing and drying cycle, which is usually several minutes, is therefore eliminated, and replaced with the much shorter dead time, of only a few tens of seconds, needed for changing between heads.