GB2512949A - A Method and Apparatus for Automatically Sampling an Individual Sample from an Array of Samples - Google Patents

Abstract

A method of individually sampling a sample comprising the use of an automated sampling apparatus to: convey a clean sampling pin to a source location and contacting the tip of the pin with the sample; conveying the pin to a target position and contacting the tip of the pin with a target location; and conveying the used pin to a discard location and discarding the used pin. Also claimed is a sampling apparatus comprising: an automated tool arranged to automatically perform the method above. Also claimed is a tool module for an automated sampling apparatus comprising: a means to mechanically and electrically connect the tool module to an automated tool arm of a sampling apparatus; and a tool carriage having means for holding a main body portion of a sampling pin. Also claimed is a sampling pin for an automated sampling apparatus comprising: an elongate body with a tip portion adapted to contact a sample to pick up a portion of the sample; and an expanded radial portion between the ends of the pin enabling it to be supported by an automated tool of a sampling apparatus.

Description

A Method and Apparatus for Automatically Sampling an Individual Sample from an Array of Samples.

The invention relates generally to a method and apparatus for automatically sampling an individual sample from an array of samples. The invention relates more particularly, but not exclusively, to automatically sampling one or more individual samples from one or more arrays of samples carried in one or more sample containers or plates.

Background

One way to try and determine the genetic functionality of an organism is by genetic sequencing and comparison. Much can be determined by reading an organism's genome sequence and comparing it with that of another, or by comparing the sequence of an individual's healthy cell with that of a cancerous cell. However, because there are so many variables at play, the results are complicated to translate. Furthermore, gene sequencing is time consuming and expensive.

Another approach is by experimentation. Genetic experimentation on humans is, for the most part, illegal and so biological models' are commonly used. For example, monkeys, rabbits, mice or fruit flies are commonly used as test organisms. However, since all living things have been shown to have evolved from the same genetic source material, other much simpler organisms exist which are known to have a considerable number of genes which are identical to those in humans. One such organism is yeast.

Yeast is a member of the fungi family. It shares about one quarter of its six thousand genes with those from human cells. Since this single-cellular organism is much older in evolutionary terms than humans, it can be assumed that the shared genes are fundamental to cell health. Yeast reproduces in a matter of hours and can do so both sexually and asexually. Most yeasts are not pathogenic and so are not dangerous to use.

Yeast colonies are small so many experiments can easily be conducted in a controlled fashion in a standard Petri dish or rectangular-format standard sample plate or container.

For these reasons, yeast is a powerful and popular model organism for study, although it is not the only one. In fact, yeast was fully sequenced before the human genome and more is known about the function of yeast genes than any other organism. Furthermore, valuable experimental resources, such as libraries ("knockout collections") of modified strains, are readily and commercially available.

Due to the aforementioned complexity in deciphering an organism's genetic code, vast experimentation and data collection is necessary. A single question such as "Which genes work closely with one particular query gene?" requires mating multiple copies of the query strain with each of the genetic variants in one of the six thousand-strong knockout collections. Perform this experiment four times to enhance statistical accuracy and this requires twenty-four thousand experiments to be conducted. Asking this simple question of each of the six thousand yeast genes then requires one hundred and forty four million experiments. Any variation of the initial question caused by introducing a query drug or by modifying the environmental conditions requires the experiments to be repeated.

Consequently, to enable large numbers of experiments of this type to be successfully conducted requires automation for speed and accuracy. This need is to some degree addressed by the use of automated sampling apparatuses that enable whole source plate arrays to be pinned or replicated on target plate arrays automatically and at high speed.

One such apparatus is described in US2007/0123999. This discloses an automated sampling apparatus for pinning whole arrays of samples. It comprises a print head having a plurality of floating pins arranged in an array for pinning whole arrays of samples from a source plate to a target plate. The pins form part of the print head such that, after each use, the print head as a whole including the pins is required to be cleaned at a wash station and sterilization unit betore re-use.

In addition to pinning or replicating whole arrays of samples, there is sometimes a desire to select one or more particular samples, e.g. yeast colonies, of special interest from an array in a source plate and transter these to a new array on a target plate. This is sometimes referred to as "cherry picking".

US2007/0123999 also discloses a module for the automated sampling apparatus for cherry picking' some samples from a source plate array and transferring these to a target plate array. The module comprises an array of separately selectable pins mounted in a print head. Each of the pins is spring-biased to an up position within the print head.

The module includes an actuation mechanism comprising a row of pneumatic or electrical actuators. The actuation mechanism is arranged to move along the print head to align with a selected column of the selectable pins. Operation of one or more of the actuators causes respective pins in the selected column to be pushed down into contact with respective samples in a source plate. These one or more samples can then be transferred to a target plate.

This apparatus exhibits a number of significant disadvantages. One problem is that it is necessary to clean and sterilize all of the selectable pins in the print head before any of the pins can be re-used. Another problem is that, because of its construction and manner of operation, it will, as work progresses, be carrying an increasing number of used and therefore contaminated, pins directly above both the source and target plates. Thus, when picking or printing, the print head will be lowered and raised directly over the source and target plates with the inherent risk that contaminants on the dirty pins may drop onto the source or target plates, especially if there are any vibrations from the pin actuators.

Consequently, the construction and manner of operating the cherry picking' module described in US2007/0123999 renders risk of contamination of the sample plates and the apparatus itself high. Furthermore, the construction of the module with the array of spring-loaded selectable pins is complicated and thus expensive to manufacture. The lengthy cleaning process necessary for cleaning the spring-loaded pins risks damaging the delicate pins and thereby affecting both their accurate placement and ability to slide when actuated.

General.

Preferably the invention mitigates or obviates to some degree one or more problems associated with known sampling methods and sampling apparatuses.

This may be met by the combination of features of the main claims; the sub-claims disclose further advantageous embodiments of the invention.

Preferably the invention provides an improved method and apparatus for automatically sampling one or more individual samples from an array of samples whilst reducing potential contamination of the sampling apparatus.

Preferably the invention provides an improved method and apparatus for automatically sampling one or more individual samples from an array of samples comprising biological, biochemical or chemical samples such as Yeast, bacteria or other types of cells, DNA, RNA or protein solution samples that are carried in one or more sample containers or plates.

One skilled in the art will derive from the following description other objects of the invention. Therefore, the foregoing statements of object are not exhaustive and serve merely to illustrate some of the many objects of the present invention.

Sum mary.

In one aspect, the invention may provide a method of automatically and sequentially cherry picking' individual samples from one or more arrays of such samples and printing the individually picked samples at predetermined positions in a target sample plate. The method may involve using an automated tool of a sampling apparatus to automatically convey a clean sampling pin to a position of a selected sample among a plurality of samples at a source location to pick up a portion of the selected sample. The tool then conveys the pin to a predetermined target position in the target sample plate provided at a target location to thereby transfer some of said portion of said selected sample to the predetermined target position. The tool then removes the used pin from the vicinity of the target location. The tool may be arranged to remove the used pin such that it is not conveyed back over the target sample plate or the source location. The tool may be arranged to discard the used pin prior to collecting a clean pin for a next sampling operation.

In a first main aspect, the invention may provide a method in a sampling apparatus of individually sampling a sample from a plurality of samples located at a source location, the method comprising using an automated tool of the apparatus to automatically perform the steps of: conveying a clean sampling pin to a position of a selected sample at the source location and causing a tip portion of said pin to come into contact with the selected sample to pick up a portion of said selected sample on said pin tip portion; conveying said pin to a predetermined target position at a target location and cause said tip portion of the pin to contact the target location to thereby transfer some of said portion of said selected sample from the pin tip portion to the predetermined target position, the pin now comprising a used pin; and removing the used pin from the target location and conveying it to a discard pin location where the tool discards the used pin.

Preferably, prior to discarding the used pin, the used pin is not conveyed by the automated tool back over the target location or the source location.

In a second main aspect, the invention may provide a method in a sampling apparatus of individually sampling a sample from a plurality of samples located at a source location, the method comprising using an automated tool of the apparatus to automatically perform the steps of: conveying a clean sampling pin to a position of a selected sample at the source location and causing a tip portion of said pin to come into contact with the selected sample to pick up a portion of said selected sample on said pin tip portion; conveying said pin to a predetermined target position at a target location and causing said tip portion of the pin to contact the target location to thereby transfer some of said portion of said selected sample from the pin tip portion to the growth medium at said predetermined target position, the pin now comprising a used pin; and removing the used pin from the target location such that, once the used pin has been moved away from the target location, it is not conveyed by the automated tool back over the target location or the source location.

By controlling the automated tool not to carry the used pin back over one or both of the target location and source location, this reduces the possibility of a used pin contaminating the individual samples printed at the target location and/or the plurality of samples provided at the source location.

Preferably, the tool is controlled to discard the used pin at a location away from the target location and/or source location. Discarding a used pin prior to performing a further sampling operation also reduces the likelihood of contamination within the sampling apparatus.

The tool may be controlled to discard the used pin by releasing the pin to fall into a used pin container. In this arrangement of the apparatus, used pins collected in the used pin container can later be cleaned and sterilized for later use if the pins are of a type

suitable for re-use.

In a preferred arrangement, the tool may be controlled to discard the used pin by placing said used pin in a pin receptacle in a pin cartridge, said pin cartridge having an array of pin receptacles for receiving pins. This allows used pins to be collected in a manner that enables them to be more easily handled, cleaned and sterilized in batches for later re-use and prevents the need for the labour intensive manual handling of individual used pins as in the case where the used pins are dropped into a used pin container.

Preferably, after the tool has discarded the used pin, the method further comprises: controlling the tool to collect a clean sampling pin from a clean pin collection location and repeating the method steps of the first main aspect of the invention or the method steps of the second main aspect of the invention for another sample at the source location. The methods of the first and second main aspects of the invention are adapted to a sequential process of picking up individual samples from the source location for printing at the target location.

Preferably also, the clean sampling pin is held ready for collection at said clean pin collection location with its tip portion maintained in a sterile condition. Whilst the sampling apparatus of the invention can comprise a generally sealed unit to provide a clean working environment, it may be beneficial to store clean pins at the collection location in a manner where their tips are maintained in a sterile condition thereby preventing said pin tips becoming contaminated by air-borne contaminants.

Preferably, the clean pins are stored at the collection location in a cartridge adapted to enable pins to be individually picked out by the automated tool, where said cartridge contains a plurality of clean pins arrayed within said cartridge.

The tool is arranged such that it can hold a pin in such a manner that the pin or a pin member of the pin can slide upwardly under its own weight when its tip portion contacts a surface such as a growth medium in a sample plate or container.

Where the pin tip is to be brought into contact with a solid growth medium such as agar, the surface area of a face of the tip portion of the pin which contacts with the surface of the growth medium may be sized with respect to the weight of the pin or the pin member so as to only exert on the surface of the growth medium a pressure that is equal to or less than a predetermined threshold pressure. The predetermined threshold pressure is preferably chosen based on a type or characteristic of the growth medium.

For example, the threshold pressure may be chosen as a pressure at which the surface of the growth medium can support the weight of the pin or pin member over the area of contact between the pin or pin member and the growth medium without the surface of the growth medium being breached or broken.

Preferably, the sampling apparatus has a computer implemented process controller for controlling automatic operation of the automated tool and preferably also a graphical user interface for enabling a human operator to enter control inputs to the process controller to control automatic operation of the automated tool. In one mode of operation, one or more samples of the plurality of samples at the source location to be individually sampled are manually selected by a human operator through control inputs inputted by the human operator into the process controller via the user interface. In another mode of operation, one or more samples of the plurality of samples at the source location to be individually sampled are identified for selection by uploading data to the computer processor controller, said data identifying source positions of said one or more samples to be individually sampled. The data may uploaded to the processor controller by any suitable means including via a communication link with the apparatus or by a physical medium such as a flash memory stick.

For ease of automation, the plurality of samples at the source location may be arranged in an array within a sample plate and said sample plate may be automatically loaded at the source location prior to the automated tool being controlled to automatically individually sample a selected one or more of the samples in the sample plate. Similarly, the target location may be loaded with a sample plate prior to the automated tool being controlled to automatically individually sample a selected one or more of the plurality of samples at the source location, said sample plate being capable of receiving an array of individually sampled samples.

In another aspect of the invention, the methods of the first and second main aspects of the invention may include the steps of: at the source location, loading a first sample plate comprising a first array of samples; at the target location, loading a sample plate capable of receiving an array of individually sampled samples at target positions in said sample plate; individually sampling one or more preselected samples in the first array of samples in the first sample plate; individually printing portions of said sampled one or more preselected samples in the first array of samples to respective predetermined target positions in the sample plate; at the source location, loading a second sample plate comprising a second array of samples; individually sampling one or more preselected samples in the second array of samples in the second sample plate; and individually printing portions of said sampled one or more preselected samples in the second array of samples to respective predetermined target positions in the target source sample plate.

This aspect of the invention enables individual samples from a plurality of source sample plates to be individually and sequentially printed to a single target sample plate and arrayed in a predetermined manner within said sample plate. This provides a very effective way of cherry picking' individual samples from multiple arrays of samples.

In a third main aspect, the invention may provide a sampling apparatus for individually sampling a sample from a plurality of samples located at a source location within the apparatus, the apparatus comprising an automated tool arranged to automatically: convey a clean sampling pin to a position of a selected sample at the source location and cause a tip portion of said pin to come into contact with the selected sample to pick up a portion of said selected sample on said pin tip portion; convey said pin to a predetermined target position at a target location and cause said tip portion of the pin to contact the target location to thereby transfer some of said portion of said selected sample from the pin tip portion to the predetermined target position, the pin now comprising a used pin; and remove the used pin from the target location and convey it to a discard pin location where the tool discards the used pin.

In a fourth main aspect, the invention may provide a sampling apparatus for individually sampling a sample from a plurality of samples located at a source location within the apparatus, the apparatus comprising an automated tool arranged to automatically: convey a clean sampling pin to a position of a selected sample at the source location and cause a tip portion of said pin to come into contact with the selected sample to pick up a portion of said selected sample on said pin tip portion; convey said pin to a predetermined target position at a target location and cause said tip portion of the pin to contact the target location to thereby transfer some of said portion of said selected sample from the pin tip portion to the predetermined target position, the pin now comprising a used pin; and remove the used pin from the target location such that, once the used pin has been moved away from the target location, it is not conveyed by the automated tool back over the target location or the source location.

In a fifth main aspect, the invention may provide a tool module for an automated sampling apparatus, the tool module comprising: means for mechanically and electrically connecting the tool module to an automated tool arm of the sampling apparatus; and a tool carriage having means for holding a main body portion of a sampling pin whereby at least a tip portion of the sampling pin extends below the tool carriage to enable said tip

S

portion to be lowered into contact with a sample and wherein the pin is held by the tool carriage in such a manner that the pin or a pin member of the pin can slide upwardly under its own weight when its tip portion contacts a sample.

The means for holding a main body portion of a sampling pin may comprise a latch which engages with an underside of a radially expanded portion of the pin to thereby hold the pin under its own weight. The latch may comprise at least one generally horizontally extending elongate latch member arranged to engage the underside of said radially expanded portion of the pin. A free end of the latch member may describe an arctate movement when the latch moves from its open to closed positions to pick up a sampling pin, the arctate movement comprising a combination of a linear movement of the free end of the latch member parallel to a face of the tool carriage and an inward movement towards the tool carriage to constrict a passage formed by a side of the latch member and the face of the tool carriage.

The tool carriage may have a vertically extending guide which engages with a sampling pin to guide vertical movement of the sampling pin relative to the tool carriage.

The guide may comprise a V or U shaped groove or it may comprise a virtual V or U shaped groove formed by a pair of vertically extending, spaced apart, parallel rod members.

Preferably, the tool module further comprises sensing means for determining when a sampling pin held by the tool carriage has slid upwardly under its own weight when its tip portion contacts a sample or a growth medium.

In a sixth main aspect, the invention provides a sampling pin for an automated sampling apparatus, the pin comprising: an elongate body with a tip portion adapted to contact a sample to pick up a portion of said sample; and a first expanded radial portion intermediate its ends to enable the pin to be supported by an automated tool of the sampling apparatus.

The sampling pin may have a second expanded radial portion adjacent one of its ends, said second expanded radial portion being adapted to contact a vertically extending guide of the automated tool of the sampling apparatus whereby the pin or a pin member of the pin can move slidably along the guide under its own weight when a tip portion of the pin is lowered into contact with a growth medium. The sampling pin may also have a third expanded radial portion adjacent the other of its ends, the third expanded radial portion also adapted to contact a vertically extending guide of the automated tool of the sampling apparatus. At least one of the second and third expanded radial portions of the pin may have a width or diameter larger than that of the first expanded radial portion. One of the second and third expanded radial portions of the pin may have a depth greater than that of the other of the second and third expanded radial portions.

In one arrangement, the elongate body of the pin is hollow and is adapted to receive an elongate pin member, said pin member being slidably received in the hollow such that a tip portion of the pin member extends below an end of the pin, said tip portion of the pin member comprising the tip portion of the pin. In this arrangement, the pin member may have a head portion of greater diameter than the hollow, said head portion of the pin member being adapted to be supported in a recess provided in an upper expanded radial portion of the pin.

In a seventh main aspect, the invention may provide a sampling pin cartridge comprising a plurality of apertures in a tray member, said apertures arranged in said tray member in an array and each aperture adapted to receive a tip portion of a sampling pin to support said sampling pin in a manner such that said pin can be individually picked out of the cartridge by an automated tool of a biological sampling apparatus.

In an eighth main aspect, the invention may provide a computer readable medium carrying machine readable instructions executable by a processor of a computer, said machine readable instructions for implementing in an automated sampling apparatus the steps of the methods of any the first and second main aspects of the invention.

The summary of the invention does not necessarily disclose all the features essential for defining the invention; the invention may reside in a sub-combination of the disclosed features.

Brief Description of the Drawings.

The foregoing and further features of the present invention will be apparent from the following description of preferred embodiments which are provided by way of example only in connection with the accompanying figures, of which: Figure 1 is a schematic layout diagram of an automated sampling apparatus; Figure 2 is a schematic layout diagram of another automated sampling apparatus; Figure 3 is a schematic layout diagram of a modified automated sampling apparatus in accordance with the invention; Figure 4 is a perspective view from one side of a tool module in accordance with the invention; Figure 5 is a perspective view from another side of a tool module in accordance with the invention; Figure 6 is a top plan view of a tool module in accordance with the invention; Figure 7 is a front view of a tool module in accordance with the invention; Figure 8(a) is a front perspective view of a tool carriage in accordance with the invention showing a latch mechanism in a closed position; Figure 8(b) is a front perspective view of a tool carriage in accordance with the invention showing a latch mechanism in an open position; Figure 9 is an enlarged view of a part of the latch mechanism and guide of the tool carriage in accordance with the invention showing a pin held in the latch mechanism; Figure 10 is an enlarged side view of a part of the latch mechanism and guide of the tool carriage in accordance with the invention showing a pin held in the latch mechanism; Figure 11 is a side view of a sampling pin in accordance with the invention; Figure 12(a) is an enlarged top view of a part of the latch mechanism and guide of the tool carriage in accordance with the invention showing a pin held in the latch mechanism with the latch mechanism in a closed position; Figure 12(b) is an enlarged top view of a part of the latch mechanism and guide of the tool carriage in accordance with the invention with the latch mechanism in an open position; Figure 13 comprises a number of views of a modified sampling pin in accordance with the invention; Figure 14 is a schematic view of a sampling process to create a target array from a plurality of source arrays in accordance with the invention; Figure 15 is an exploded perspective view of a pin cartridge in accordance with the invention; Figure 16 is a perspective view of component pads of the cartridge of Fig. 15; and Figure 17 is a perspective view showing an underside of a component part of the cartridge of Fig. 15.

Detailed Description.

The following description is of preferred embodiments by way of example only and without limitation to the combination of features necessary for carrying the invention into effect.

Reference in this specification to "one embodiment" or "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the invention. The appearances of the phrase "in one embodiment" in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments. Moreover, various features are described which may be exhibited by some embodiments and not by others. Similarly, various requirements are described which may be requirements for some embodiments but not other embodiments.

The terms "pick" or "pick up" as used herein generally refer to the action of causing a pin to come into contact with a sample such as a yeast colony such that a part of the sample, e.g. some cells, transfers onto the pin. The term "print" is used herein to describe the action of causing a pin carrying a microbial sample or the like to contact with a position at a target location to thereby transfer part, e.g. some cells, of the sample onto the position at the target location.

Fig. 1 shows a schematic layout diagram of an automated sampling apparatus capable of automatically pinning or replicating whole microbial arrays of samples such as yeast colonies or the like at relatively high speed.

The sampling apparatus 10 comprises an automated tool 12 carrying a print head 14. The automated tool 12 can move the print head 14 in one or more dimensions in space. The print head 14 is capable of carrying an array of sampling pins 16 which it may collect as a pad 18 of pins at a pin pad collection station 20. The pin pad collection station may include a cleaning and sterilization unit, although the cleaning and sterilization unit may be separate from the pin pad collection station 20.

The apparatus 10 includes a source location 22 where an array of samples in a sample plate can be automatically loaded/withdrawn from/to a source sample plate station 24. Also included is a target location 26 where a target sample plate can be automatically loadedlwithdrawn from/to a target sample plate station 28.

In operation, a source sample plate containing a plurality of samples such as yeast colonies arranged in a densely packed array is loaded onto the source location 22. A target sample plate containing a growth medium is loaded onto the target location 26.

The growth medium is capable of receiving an array of samples. The growth medium may be a liquid growth medium in which case the target plate array is defined by a pattern of wells formed in the plate base. In the case of a solid growth medium such as agar, the surface of the agar receives the plurality of samples.

The print head 14 picks up a pin pad 18 comprising an array of clean, sterilized sampling pins 16 from the collection station/sterilization unit 20. The automated tool 12 drives the print head 14 to the source location 22 where it carefully lowers the print head 14 to drive the sampling pins into contact with the array of samples, e.g. yeast colonies, on the source sample plate. Each pin contacts a respective sample and a part of such sample transfers onto the pin.

Before the print head 14 is lowered, a source location cover lifting module 30 may be utilized to lift a cover from the source sample plate and hold said cover out of the path of the print head 14 while it is lowered and then return the cover to the source sample plate. Sample plates are normally covered to reduce the risk of contamination by airborne contaminants.

The tool 12 then drives the print head 14 to the target location where it lowers the print head to print, i.e. transfer, parts of the samples from the array of pins 16 into or onto the growth medium of the target sample plate. Consequently, the transferred samples replicate on the target sample plate the array of samples of the source sample plate.

A target location cover lifting module 32 may be provided for removal and replacement of a cover of the target sample plate.

Once the sample printing at the target sample plate is completed, the tool 12 drives the print head 14 to the pin collection station/sterilization unit 20 to release the pin pad 18 for cleaning and sterilization and to pick up a replacement pin pad for another sample array pick and print process.

The schematic layout diagram of Fig. 1 is representative of an automated sampling apparatus. However, it will be understood that the schematic layout of Fig. 1 is not a strict spatial representation of such an apparatus and that the apparatus may have a different spatial configuration and may include additional modules for performing additional functions. However, the above described operation of pinning or replicating a microbial array or the like from a source plate to a target plate is generally representative of the automated pinning or replicating process performed by such apparatuses.

Referring to Fig. 2, this shows a schematic layout diagram of another automated sampling apparatus 110 for pinning or replicating whole arrays of samples such as whole arrays of yeast colonies. It is similar in structure to the apparatus of Fig. 1, but differs in that it employs already prepared packs of sterilized pin pads and therefore negates the need for the apparatus 110 itself to delay operations whilst it awaits a used pin pad 118 being cleaned and sterilized within the apparatus. Packs of pin pads 118 are loaded into the apparatus 110 via a pin pad hopper 134 and made available for picking up by the print head 114 at the pin pad collection station 120. The hopper 134 may include an autoclave forfurther sterilizing the pin pads 118 prior to use. When a pin pad 118 has been used, the tool 112 drives the print head 114 to a pin pad dump station 136 where the print head 114 is controlled to release the used pin pad 118 which then drops into a pin pad dump container 138. Used pin pads 118 can be removed from the dump container 138 of the apparatus 110 for cleaning and sterilizing at another location. In one embodiment, at least the pins 116 of the pin pads 118 are disposable. Consequently, the pins 116 are replaced in the pin pads 118 when the pads are removed for cleaning.

In operation, a source sample plate containing a plurality of samples such as yeast colonies arranged in a densely packed array is loaded onto the source location 122 from a loading station 124. A target sample plate containing a growth medium is loaded onto the target location 126 from another loading station 128. The print head 114 picks up a pin pad 118 from the collection station 120. The automated tool 112 drives the print head 114 to the source location 122 where it lowers the print head 114 to drive the sampling pins 116 into contact with the array of samples on the source sample plate. The cover lifting module 130 lifts a cover from the source sample plate and holds said cover out of the path of the print head 114 as necessary and then returns the cover to the source sample plate.

The tool 112 then drives the print head 114 to the target location where it lowers the print head to print parts of the samples from the array of pins 116 into or onto the growth medium of the target sample plate. A target location cover lifting module 132 removes and replaces a cover of the target sample plate as necessary.

Once the sample printing at the target sample plate is completed, the tool 112 drives the print head 114 to the dump station 136 to discard the used pin pad 118. The tool 112 then drives the print head 114 back to the collection station 120 to pick up a clean pin pad 118 ready to repeat the pinning or replicating process.

The schematic layout diagram of Fig. 2 is representative of applicant's automated sampling apparatus manufactured under the trade name RoToR HDATM. The schematic layout of Fig. 2 is not, however, a strict spatial representation of applicant's RoToR HDATMapparatus. The RoToR HoATMapparatus has a different spatial configuration to that schematically illustrated in Fig. 2 and may include additional modules for performing additional functions. However, the above described operation of pinning or replicating a whole array from a source plate to a target plate is generally representative of the automated pinning or replicating process performed by applicant's RoToR HDATM automated sampling apparatus.

In this apparatus 110, the print head 114 is easily manually removable from the automated arm 112. Consequently, this apparatus 110 and the apparatus 10 of Fig. 1 can be modified with a suitable replacement print head tool module according to the invention as will be described hereinafter for individually picking and printing one or more particular samples, e.g. yeast colonies, of special interest from one or more arrays in one or more source plates and transferring these individually to a new array on a target plate, i.e. to "cherry pick".

Fig. 3 provides a schematic layout of applicant's automated sampling apparatus of Fig.2 modified in accordance with the invention to enable it to perform individual picking and printing of samples from one or more source plates to a target plate, although it will be understood that the same modification could be made to the apparatus 10 of Fig. 1 still in accordance with the invention.

The apparatus 110' of Fig. 3 is modified by replacing the print head on the automated tool 112 by a tool module 150 having a tool carriage 152. The tool carriage is adapted to carry a single sampling pin 116'. The tool carriage is mounted on the tool module by a cross-rail (Fig. 4) such that the tool carriage 152 can move in a horizontal direction relative to the tool module 150 to increase the range of movement of a pin 116' for bringing it into precise contact with a sample at the source location 122 or a target position at the target location 126.

In operation, a first source sample plate containing first a plurality of samples such as yeast colonies arranged in a densely packed array is loaded onto the source location 122 from a loading station 124. A target sample plate containing a growth medium is loaded onto the target location 126 from another loading station 128. The tool carriage collects a pin 116' from the collection station 120. The automated tool 112 drives the tool carriage 152 to the source location 122 where it lowers the tool carriage 152 to drive the sampling pin 116' into contact with a selected one of the array of samples on the source sample plate. The cover lifting module 130 lifts a cover from the source sample plate and holds said cover out of the path of the tool carriage 152 as necessary and then returns the cover to the source sample plate. Where necessary, to obtain alignment of the sampling pin 116' with the selected one of the samples in the source plate, the tool carriage 152 may be controlled to move horizontally relative to the tool module 150 and thus move relative to the automated tool armi 12.

The tool 112 then drives the tool carriage 152 to the target location where it lowers the carriage 152 to print a part of the sample from the pin 116' into or onto the growth medium of the target sample plate. Again, the tool carriage 152 can be moved to better align the pin 116' with a target position if that is required. A target location cover lifting module 132 removes and replaces a cover of the target sample plate as necessary.

Once the sample printing at the target sample plate is completed, the tool 112 drives the carriage 152 to a pin discard station 136' to discard the used pin 116'. The tool 112 then drives the carriage 152 back to the collection station 120 to pick up a clean pin 116' ready to repeat the pinning process for a different selected one of the samples of the source plate or another source plate.

It will be understood that the tool carriage 152 carries a single sampling pin 116' and thus picking and printing samples from one or more source plates to a target plate is a sequential process whereby individual samples are transferred individually from the source plate(s) to the target plate. This affords a high degree of selectability for a user in selecting samples such as yeast colonies of special interest from among pluralities of other samples.

It will also be understood that the arrowed lines in Fig. 3 indicative of movement pathways of the apparatus's components are merely representative of start and end points of such pathways and that the components of the apparatus 110' are not confined to such pathways. For example, the automated tool 112 which may be moveable in up to three dimensions of space can be controlled to take a shortest pathway between two locations and yet be controlled to take a longer pathway where doing so has a beneficial effect such as reducing the likelihood of contamination of the apparatus or parts of it.

The individual picking and printing process using single replaceable pins 116' as described above can be repeated until the target plate array is completed or until enough such samples have been individually picked and printed as required. Fig. 14 illustrates the process where source plate arrays 160, 162, 164, 166 are sequentially loaded to the source location 122 of the sampling apparatus 110' and a small number of selected samples (shown ringed in Fig. 14) are individually picked from each source plate and individually printed into one or more arrays 170, 172, 174, 176 in a target plate 180 at the target location 126. In the example of Fig. 14 four source plate arrays 160, 162, 164, 166 are sampled and the individual samples sequentially transferred to respective arrays 170, 172, 174, 176 in a single target plate 180, although other configurations of the sample arrays are, of course, possible. The source plate arrays may be loaded using a rotating

table (not shown).

In one embodiment, the tool carriage 152 is controlled to discard the used pin 116' by releasing the pin to fall into a used pin container 138', but in a preferred arrangement, the carriage tool 152 is controlled to discard the used pin 116' by placing said used pin 116' in a pin receptacle in a pin cartridge which may be provided in an indexable slide mechanism located at or near the collection station 120 or elsewhere in the apparatus 110'. The slide mechanism may also contain one or more clean pin cartridges. The used pin cartridge may have an array of pin receptacles for receiving pins. The used pin cartridge once filled with used pins can then be removed from the apparatus for processing such as cleaning and/or replacing the used pins. The pins may be disposable pins.

The sampling apparatus 110' has a computer implemented process controller 190 running custom software for controlling automatic operation of the automated tool 112, tool module 150 and tool carriage 152 and preferably also a graphical user interface 192 for enabling a human operator to enter control inputs to the process controller 190 to control automatic operation of the automated tool 112 and tool carriage 152. In one mode of operation, one or more samples of the plurality of samples at the source location 122 to be individually sampled are manually selected by a human operator through control inputs inputted by the human operator into the process controller 190 via the user interface 192.

In this mode of operation, the process controller 190 also enables a user to specify positions of colonies on an unstructured lawn of samples in a sample plate for automatic and precise picking and printing. In another mode of operation, one or more samples of the plurality of samples at the source location 122 to be individually sampled are identified for selection by uploading data to the computer processor controller 190, said data identifying source positions of said one or more samples to be individually sampled. The data may be uploaded to the processor controller by any suitable means including via a communication link between the apparatus and another device such as a personal computer or the like connected thereto by a network, or by a physical medium such as a flash memory stick or other data storage medium. The data may be uploaded in a file format such as.csv (comma separated value) or any other suitable data file format. When the user imports a file into the process controller 190, the software transposes the positions of the colonies on all the plates the user has provided into a full routine that, apart from loading plates and pin cartridges, requires no further user interaction to carry out all pinning operations detailed in the data file. This automation is vital as it minimizes human errors, and speeds the process of picking and pinning colonies up hugely and in a highly economical and efficient way.

In one embodiment, the clean sampling pin 116' is held ready for collection at said clean pin collection location 120 with its tip portion maintained in a sterile condition.

In a preferred embodiment, the clean pins are stored at the collection location 120 in a cartridge adapted to enable the pins 116' to be individually picked out by the tool carriage 152, where said cartridge contains a plurality of clean pins arrayed within said cartridge. A boftom tray of the cartridge may contain a liquid for maintaining the tip portions of the pins in a sterile condition.

Referring to Figs. 4 to 7, shown is the tool module 150 for the automated sampling apparatus 110' of Fig. 3. The tool module 150 is attached to the automated tool arm 112 using a magnetically coupled quick change base plate 200 of a similar type to that used to connect the print head 114 of the apparatus 110 of Fig. 2 to the automated tool 112.

Consequently, changeover of the sampling apparatus between normal whole array pinning and individual pinning according to the invention can be achieved easily and rapidly and without the use of tools, whilst the kinematic nature of the quick change base plate 200, ensures a high degree of accuracy/repeatability.

The tool module 150 comprises a housing 202 containing a circuit board equipped with a power supply module, various sensors and interface electronics that support a dedicated microprocessor is also provided on the tool module's circuit board. This microprocessor runs specially developed firmware that manages functions of the tool module 150 and tool carriage 152 as well as communication with software running on the process controller 190.

The tool module 150 has a first main electrical power and signal connector 204 (Fig. 6) connecting it to the automated tool arm 112 and the process controller 190. A second electrical power and signal connection 206 is provided between the automated tool 112 or tool module 150 and the tool carriage 152. Furthermore, a pneumatic air supply connector 208 is provided on the tool carriage 152.

The tool carriage 152 is carried on a linear cross-rail 210 on an end face of the tool module 150 to provide extra range of Y-axis travel for a sampling pin 116' as may sometimes be required by individual sampling operations. Travel of the tool carriage 152 on the rail 210 is driven by a servo-motor controlled by the process controller 190 and/or tool module microprocessor and connected to the carriage 152 by a flexure coupling to avoid the risk of damage when handled by the user during changeover between normal whole array sampling and individual sampling operations.

The tool carriage 152 has a latch mechanism 212 for holding the main body portion of a sampling pin 116' whereby at least a tip portion 116'a of the sampling pin extends below the tool carriage to enable said tip portion 11 6'a to be lowered into contact with a sample. The pin 116' is held by the tool carriage 152 in such a manner that the pin 116' or a pin member (Fig. 13) of the pin can slide upwardly under its own weight when its tip portion contacts a sample or a solid growth medium.

The latch mechanism 212, more easily seen in Figs. 8(a) and (b), engages with an underside of a radially expanded portion or spool 230 (FIG. 11) of the pin 116' to thereby hold the pin 116' under its own weight. The latch mechanism 212 may comprise at least one generally horizontally extending elongate latch member 214 arranged to engage an underside of said spool 230 of the pin 116'. Preferably, the latch mechanism 212 comprises two latch members 214 which are co-mounted to a latch plate part of the mechanism 212 and are arranged to be spaced part by a distance that only allows contact with the centre spool 230 of the pin 116', to be parallel and to move in unison. A free end of the latch member or members 214 may describe an arctate movement when the latch mechanism 212 moves from its open position (Figs. 8b and 12b)to its closed position (Figs. 8a and 12a) to pick up a sampling pin 116', the arctate movement comprising a combination of a linear movement of the free end of the latch member or members 214 parallel to an end face of the tool carriage 152 and an inward movement towards the tool carriage end face to constrict a passage 216 formed by a side or sides of the latch member or members 214 and the guide 218, more particularly the guide rods 220 of the tool carriage 152.

The latch mechanism 212 which is used to pick-up and discard a pin 116' is operated by a spring-return, single action pneumatic cylinder controlled by a valve manifold on the sampling apparatus 110'. The latch mechanism 212 is kinematically seated in a closed position and a return spring is supplemented by a vacuum to ensure the mechanism remains seated and the pin 116' is retained during rapid acceleration or stirring actions of the automated tool arm 112. The latch mechanism 212 is opened by a blow function whereby a spring plunger acting on the head of a spherical member causes an arctate motion to the latch mechanism 212 to facilitate an optimum pin pick up and pin drop action.

The tool carriage 152 has a vertically extending guide 218 in its end face which engages with a sampling pin 116' when held by the latch mechanism 212 to guide vertical movementofthe sampling pin 116' relative to the tool carriage 152. The guide 218 may comprise a V or U shaped groove or it may comprise a virtual V or U shaped groove formed by a pair of vertically extending, spaced apart, parallel rod members 220.

The tool carriage 152 is arranged such that it can hold a pin 116' in such a manner that the pin or a pin member of the pin can slide upwardly under its own weight when its tip portion 116'a contacts a surface such as a growth medium in a sample plate or container.

Where the pin tip 116'a is to be brought into contact with a solid growth medium such as agar, the surface area of a face of the tip portion of the pin 116' which contacts with the surface of the growth medium may be sized with respect to the weight of the pin or the pin member so as to only exert on the surface of the growth medium a pressure that is equal to or less than a predetermined threshold pressure. The predetermined threshold pressure is preferably chosen based on a type or characteristic of the growth medium. For example, the threshold pressure may be chosen as a pressure at which the surface of the growth medium can support the weight of the pin or pin member over the area of contact between the pin or pin member and the growth medium without the surface of the growth medium being breached or broken.

The tool carriage 152 further comprises sensing means for determining when a sampling pin 116' held by the latch mechanism 212 has slid upwardly under its own weight when its tip portion 1 16'a contacts a sample or a growth medium. In one embodiment, there are provided first and second optical sensors 222, 224 (Fig. 8(b)).

These may be located respectively at upper and lower ends of the pin guide 218.

The optical sensors 222, 224 are of a reflective type and stare' out between the guide rods 220 of the guide 218. The lower sensor 224 looks' for the reflection of the pin 116', i.e. its presence or lack of it, after the pin is discarded. The sensor 224 is adjusted so that it does not see, i.e. detect, the pin in the next row of the clean pin cartridge when the latch mechanism is collecting a clean pin. The upper sensor 222 looks' for the upper edge of the pin 116' when the pin rises relative to the upper sensor 222 as soon as the pin 116' contacts the sample or growth medium. This sensor 222 also shows whether the pin has correctly dropped down so that the process can be repeated after arrival at the target location for printing.

The upper optical sensor 222 that detects the connection of the pin 116' to a surface such as a surface of a growth medium is hard wired directly to a fast interrupt digital input on the process controller 190, which provides instantaneous collision and surface detection at all times, even if other less direct communication between the process controller 190 and the microprocessor of the tool module 150 drops out. This provides a highly reliable method of communication for the sensor 222, and is essential for allowing such complex operations as picking up a pin from a pin cartridge, and pinning to either a solid media such as agar or a liquid solution without the risk of contamination or accidental destruction of the source plates. It will be understood that the optical sensors 222, 224 could be replaced by proximity detectors depending on a characteristic of the pins such as their material of manufacture.

The tool module 150 is physically protected with a kinematically mounted bumper fender 226 that instantly reports when it becomes unseated, so causing crash' protection procedures to run in the process controller 190. The seating of the bumper fender 226 is indicated by an LED indicator mounted in the end of the tool module body 202, so it is easy for the user to ensure that it the module is seated correctly after the head is changed or the bumper fender 226 is somehow disturbed.

Referring to Figs. 9 to 11, a sampling pin 116' for an automated sampling apparatus 110' according to the invention comprises an elongate body 116'b with a tip portion 116'a adapted to contact a sample to pick up a portion of said sample and at least a first expanded radial portion or spool 230 intermediate its ends to enable the pin to be supported under its own weight by the latch mechanism 212 of the tool carriage 152.

The pin 116' has three short expanded or spooi portions 230, 232, 234 of larger diameter than the main cylindrical body 11 6'b. A bottom one 234 of these spools is double the length or depth of either the other two spools or collars 230, 232. The main cylindrical body 11 6'b of the pin extends beyond this bottom spool 234 and is tapered down to provide the working tip portion 11 6'a.

The tip diameter may be such as to allow pinning to 1536 density in a standard sample plate and is long enough to reach the bottom of 96 and 384 standard multi-Well plates. A bottom face of the bottom spool 234 enables the pin 116' to sit stably in a pin cartridge when the tip portion 11 6'a of the pin is received in a pin support aperture of the pin cartridge. The extra length of the bottom spool 234 allows a sensible margin of clearance for the latch mechanism 212 over the top of the pin cartridge when picking up a pin 116' from the pin cartridge.

The outer surfaces of the top and bottom spools 232, 234 engage with the guide rods 220 to control sliding movement of the pin 116' within the guide 218. The width or diameter of the middle spool 230 is less than that of either of the top and bottom spools 232, 234 so that it does not contact the surface of the guide rods 220 and thus does not interfere with the sliding alignment of the pin 116' within the guide 218 when the pin 116' is being held by the latch mechanism 212.

The retention of the pin 116' is preferably controlled by the two cantilevered elongate latch members 214 set horizontally across the front of the pin's main cylindrical body on each side of the central spool 230. The top latch member 214 prevents the pin 116' from rotating forward at its top end and the lower latch member 214 prevents it being pulled away from the guide 218 during stirring operations of the automated tool 112. The lower latch member 214 also acts on the centre spool 230 to pick up the pin while a sloping lower face 230a of this spool 230 imparts a force on the pin 116' so that it gravitates towards the guide rods 220 before and after pin pick-up and printing, so maximising the accurate positioning of the pin tip portion 116'a whilst allowing a sensible clearance between the two elongate latch members 214 to allow for manufacturing tolerances and accommodate variations in size between pins. Preferably, the centre spool 230 is marginally smaller than the other two spools 232. 234 so that it cannot interfere with their correct seating if the pin 116' is not perfectly straight. It is important that the latch members 214 do not impinge on the pin's main body portions as this would drastically and unpredictably alter the friction between the pin and the guide 218 thereby compromising the sliding movement of the pin under its own weight.

The arctate movement of the at two elongate members 214 of the latch mechanism 212 is such that they cause the latch members 214 to be able to gather or collect a pin 116' that is not exactly centred or standing perfectly vertical in the pin cartridge when picking up. It also enables reliable dumping of the pin as the action rapidly clears the latch members 214 away from the central spool 230 as the latch mechanism 212 opens, and does not impart any rotation to the pin 116' as it clears the latch mechanism 212.

The size, i.e. surface area, of the end face of the pin's tip portion 116'a in combination with its weight and arrival speed on contact with a growth medium is directly related to the pressure exerted by the pin tip on the surface of the growth medium. Where a user wishes to greatly increase the density of a sample array to say 6144 or greater in a standard sample plate, it is difficult to achieve this without some modification of the pin 116' as the pin 116' depicted in Figs. 9 toll is adapted to print lower sample array densities.

Referring to Fig. 13, the pin 116' of Fig. 11 can be modified as depicted in Fig. 13 such that the elongate body of the pin 116" is hollow and is adapted to receive an elongate pin member 117 in a through hole defining the hollow. The pin member 117 is slidably received in the through hole such that a tip portion 117a of the pin member 117 extends below an end of the pin 116", whose tip portion is truncated. The tip portion 1 17a of the pin member 117, which is substantially smaller than that of the tip portion 11 6'a of the pin depicted in Fig. 11, therefore comprises the tip portion of the pin 116" for greater density sample arrays, because, when the tip portion 11 7a of the slidable pin member 117 contacts a surface of a growth medium it slides up relative to the main body of the pin 116" under only its own weight and not that of the main body of the pin. The pin member 117 has a head portion 11 7b of greater diameter than that of the through hole. The head portion 11 7b of the pin member is adapted to be supported in a recess 232a provided in the upper expanded spool 232 of the pin 116".

Referring to Figs. 15 to 17, a cartridge 300 for the pins 116' comprises a plurality of apertures 302 in a tray member 304. The apertures 302 are arranged in said tray member 304 in an array and each aperture 302 is adapted to receive a tip portion of a pin to support said sampling pin in a manner such that said pin can be individually picked out of the cartridge by the tool carriage 152 latch mechanism 212.

The cartridge 300 comprises three main components, the tray member or pin holder 304, a bottom tray 306 and a cover 308. All three parts are machined from aluminium alloy, black anodised and double sealed to enable repeated autoclaving without blooming", and the parts, where necessary, may be suitably ribbed to resist warping.

The cartridge 300 is adapted to fit into and be correctly aligned and positioned by applicant's existing RoToR HDA sampling apparatus. Therefore, the bottom part of the cartridge has the same dimensions and has the same corner chamfer for orientation purposes as the standard pin pad for the apparatus of Fig. 2. A top face of the pin holder 304 and its flange are laser etched to aid in establishing the co-ordinates of the first pin where a part load of pins is desired to be used.

The bottom tray 306 is magnetically secured to the underside of the pin holder 304 and serves to prevent contamination of a loaded cartridge during use by air-currents from below, or when in transit from an autoclave. The magnets used are of a type suitable for the temperatures involved in autoclaving, as is a special epoxy resin used to encapsulate them into the tray and holder. The bottom tray 306 may also hold a quantity of fluid or the like suitable to kill off cells on the tips of used pins should it be used for this purpose or it may maintain clean pin tip portions in a sterile condition prior to use.

The cover 308 completes the cartiidge assembly 300. It is secured with two stainless thumb/socket screws 310 which enable the loaded cartridge 300 to be safely and easily carried and serves to prevent contamination after autoclaving. The top face of the cover is recessed to enable stacking of cartridges without the risk of slipping. With the cover 308 in place and the bottom tray 306 removed, the working end of the pins are exposed to facilitate easy mechanical cleaning before autoclaving if so desired as the pins are securely held whilst being below the holder's bottom edge to prevent damage.

In general, the invention provides a method of automatically and sequentially cherry picking' individual samples from one or more arrays of such samples and printing the individually picked samples at predetermined positions in a target sample plate. The method may involve using an automated tool of a sampling apparatus to automatically convey a clean sampling pin to a position of a selected sample among a plurality of samples at a source location to pick up a portion of the selected sample. The tool then conveys the pin to a predetermined target position in the target sample plate provided at a target location to thereby transfer some of said portion of said selected sample to the predetermined target position. The tool then removes the used pin from the vicinity of the target location. The tool may be arranged to remove the used pin such that it is not conveyed back over the target sample plate or the source location. The tool may be arranged to discard the used pin prior to collecting a clean pin for a next sampling operation.

The invention relates to automatically individually selecting one or more samples from an array of samples comprising biological, biochemical or chemical samples such as Yeast, bacteria or other types of cells, DNA, RNA or protein solution samples that are carried in one or more sample containers or plates.

While the invention has been illustrated and described in detail in the drawings and foregoing description, the same is to be considered as illustrative and not restrictive in character, it being understood that only exemplary embodiments have been shown and described and do not limit the scope of the invention in any manner. It can be appreciated that any of the features described herein may be used with any embodiment. The illustrative embodiments are not exclusive of each other or of other embodiments not recited herein. Accordingly, the invention also provides embodiments that comprise combinations of one or more of the illustrative embodiments described above.

Modifications and variations of the invention as herein set forth can be made without departing from the spirit and scope thereof, and, therefore, only such limitations should be imposed as are indicated by the appended claims.

In the claims which follow and in the preceding description of the invention, except where the context requires otherwise due to express language or necessary implication, the word "comprise" or variations such as "comprises" or "comprising" is used in an inclusive sense, i.e. to specify the presence of the stated features but not to preclude the presence or addition of further features in various embodiments of the invention.

It is to be understood that, if any prior art publication is referred to herein, such reference does not constitute an admission that the publication forms a pad of the common general knowledge in the art.

Claims (43)

1. Claims.1. A method in a sampling apparatus of individually sampling a sample from a plurality of samples located at a source location, the method comprising using an automated tool of the apparatus to automatically perform the steps of conveying a clean sampling pin to a position of a selected sample at the source location and causing a tip portion of said pin to come into contact with the selected sample to pick up a portion of said selected sample on said pin tip portion; conveying said pin to a predetermined target position at a target location and cause said tip portion of the pin to contact the target location to thereby transfer some of said portion of said selected sample from the pin tip portion to the predetermined target position, the pin now comprising a used pin; and removing the used pin from the target location and conveying it to a discard pin location where the tool discards the used pin.
2. 2. The method of claim 1, wherein, once the used pin has been moved away from the target location, it is not conveyed by the automated tool back over the target location or the source location.
3. 3. A method in a sampling apparatus of individually sampling a sample from a plurality of samples located at a source location, the method comprising using an automated tool of the apparatus to automatically perform the steps of: conveying a clean sampling pin to a position of a selected sample at the source location and causing a tip portion of said pin to come into contact with the selected sample to pick up a portion of said selected sample on said pin tip portion; conveying said pin to a predetermined target position at a target location and causing said tip portion of the pin to contact the target location to thereby transfer some of said portion of said selected sample from the pin tip portion to said predetermined target position, the pin now comprising a used pin; and removing the used pin from the target location such that, once the used pin has been moved away from the target location, it is not conveyed by the automated tool back over the target location or the source location.
4. 4. The method of claim 3, wherein, once the used pin has been moved away from the target location, it is conveyed by the automated tool to a discard pin location where the tool discards the used pin.
5. 5. The method of any one of claims 2 to 4, wherein the tool is controlled to discard the used pin by releasing the pin to fall into a used pin container.
6. 6. The method of any one of claims 2 to 4, wherein the tool is controlled to discard the used pin by placing said used pin in a pin receptacle in a pin cartridge, said pin cartridge having an array of pin receptacles for receiving pins.
7. 7. The method of any one of claims 2 to 6, wherein, after the tool has discarded the used pin, the method further comprises: controlling the tool to collect a clean sampling pin from a clean pin collection location and repeating the method steps of claim 1 or repeating the method steps of claims 3 and 4 for another sample at the source location.
8. 8. The method of claim 7, wherein the clean sampling pin is held ready for collection at said clean pin collection location with its tip portion maintained in a sterile condition.
9. 9. The method of claim 7 or claim 8, wherein the tool is controlled to collect a clean sampling pin from a cartridge containing a plurality of clean pins arrayed within said cartridge.
10. 10. The method of any one of claims 7 to 9, wherein the tool is controlled to collect a clean sampling pin from the clean pin location one pin at a time.
11. 11. The method of any one of the preceding claims wherein the pin is held by the tool in such a manner that the pin or a pin member of the pin can slide upwardly under its own weight when its tip portion contacts a growth medium.
12. 12. The method of claim 11, wherein a surface area of a face of the tip portion of the pin which contacts with a growth medium is sized with respect to the weight of the pin or the pin member to exert on a surface of the growth medium a pressure that is equal to or less than a predetermined threshold pressure.
13. 13. The method of claim 12, wherein the predetermined threshold pressure is dependent on a type or characteristic of the growth medium.
14. 14. The method of any one of the preceding claims, wherein the sampling apparatus has a computer implemented process controller for controlling automatic operation of the automated tool.
15. 15. The method of claim 14, wherein the sampling apparatus has a graphical user interface for enabling a human operator to enter control inputs to the process controller to control automatic operation of the automated tool.
16. 16. The method of claim 15, wherein one or more samples of the plurality of samples at the source location to be individually sampled are manually selected by a human operator through control inputs inputted by the human operator into the process controller via the user interface.
17. 17. The method of claim 14 or claim 15, wherein one or more samples of the plurality of samples at the source location to be individually sampled are identified for selection by uploading data to the computer processoi controller, said data identifying source positions of said one or more samples to be individually sampled.
18. 18. The method of any one of the preceding claims, wherein the plurality of samples at the source location are arranged in an array within a sample plate, said sample plate being automatically loaded at the source location prior to the automated tool being controlled to automatically individually sample a selected one or more of the samples in the sample plate.
19. 19. The method of any one of the preceding claims, wherein the target location is loaded with a sample plate prior to the automated tool being controlled to automatically individually sample a selected one or more of the plurality of samples at the source location, said sample plate being capable of receiving an array of individually sampled samples.
20. 20. The method of any one of claims ito 17, further comprising the steps of: at the source location, loading a first sample plate comprising a first array of samples; at the target location, loading a sample plate capable of receiving an array of individually sampled samples at target positions in said sample plate; individually sampling one or morn preselected samples in the first airay of samples in the first sample plate; individually printing portions of said sampled one or more preselected samples in the first ariay of samples to respective predetermined target positions in the sample plate; at the source location, loading a second sample plate comprising a second array of samples; individually sampling one or more preselected samples in the second array of samples in the second sample plate; and individually punting poitions of said sampled one or more preselected samples in the second array of samples to respective predetermined target positions in the target source sample plate.
21. 21. A sampling apparatus for individually sampling a sample from a plurality of samples located at a source location within the apparatus, the apparatus comprising an automated tool arianged to automatically: convey a clean sampling pin to a position of a selected sample at the souice location and cause a tip portion of said pin to come into contact with the selected sample to pick up a portion of said selected sample on said pin tip portion; convey said pin to a predetermined target position at a taiget location and cause said tip portion of the pin to contact the target location to thereby transfer some of said portion of said selected sample from the pin tip portion to the predetermined target position, the pin now comprising a used pin; and remove the used pin from the taiget location and convey it to a discard pin location where the tool discards the used pin.
22. 22. The apparatus of claim 21, wherein the tool is arranged to not convey the used pin back over the target location or the souice location after the used pin has been moved away from the target location.
23. 23. A sampling appalatus for individually sampling a sample from a pluiality of samples located at a source location within the apparatus, the apparatus comprising an automated tool arranged to automatically: convey a clean sampling pin to a position of a selected sample at the source location and cause a tip portion of said pin to come into contact with the selected sample to pick up a portion of said selected sample on said pin tip portion; convey said pin to a predetermined target position at a target location and cause said tip portion of the pin to contact the target location to thereby transfer some of said portion of said selected sample from the pin tip portion to the predetermined target position, the pin now comprising a used pin; and remove the used pin from the target location such that, once the used pin has been moved away from the target location, it is not conveyed by the automated tool back over the target location or the source location.
24. 24. The apparatus of claim 23, wherein the tool is arranged to convey the used pin to a discard pin location and discard the used pin after the used pin has been moved away from the target location.
25. 25. A tool module for an automated sampling apparatus, the tool module comprising: means for mechanically and electiically connecting the tool module to an automated tool arm of the sampling apparatus; and a tool carriage having means for holding a main body portion of a sampling pin whereby at least a tip portion of the sampling pin extends below the tool carriage to enable said tip portion to be lowered into contact with a sample and wherein the pin is held by the tool carriage in such a manner that the pin or a pin member of the pin can slide upwardly under its own weight when its tip portion contacts a sample.
26. 26. The tool module of claim 25, wherein the means for holding a main body portion of a sampling pin comprises a latch which engages with an underside of a radially expanded portion of the pin to thereby hold the pin under its own weight.
27. 27. The tool module of claim 26, wherein the latch comprises at least one generally horizontally extending elongate latch member arranged to engage the underside of said radially expanded portion of the pin.
28. 28. The tool module of claim 27, wherein a free end of the latch member describes an arctate movement when the latch moves from its open to closed positions to pick up a sampling pin, the arctate movement comprising a combination of a linear movement of the tree end of the latch member parallel to a face of the tool carriage and an inward movement towards the tool carriage to constrict a passage formed by a side of the latch member and the face of the tool carriage.
29. 29. The tool module of any one of claims 25 to 28, wherein the tool carriage has a vertically extending guide which engages with a sampling pin to guide vertical movement of the sampling pin relative to the tool carriage.
30. 30. The tool module of claim 29, wherein the guide comprises a V or U shaped groove.
31. 31 The tool module of claim 29, wherein the guide comprises a virtual V or U shaped groove formed by a pair of vertically extending, spaced apart, parallel rod members.
32. 32. The tool module of any one of claims 25 to 31, wherein it further comprises sensing means for determining when a sampling pin held by the tool carriage has slid upwardly under its own weight when its tip portion contacts sample.
33. 33. A sampling pin for an automated sampling apparatus, the pin comprising: an elongate body with a tip portion adapted to contact a sample to pick up a portion of said sample; and a first expanded radial portion intermediate its ends to enable the pin to be supported by an automated tool of the sampling apparatus.
34. 34. The sampling pin of claim 33, wherein the pin has a second expanded radial portion adjacent one of its ends, said second expanded radial portion being adapted to contact a vertically extending guide of the automated tool of the sampling apparatus whereby the pin or a pin member of the pin can move slidably along the guide under its own weight when a tip portion of the pin is lowered into contact with a growth medium.
35. 35. The sampling pin of claim 35, wherein the pin has a third expanded radial portion adjacent the other of its ends, the third expanded radial portion also adapted to contact a vertically extending guide of the automated tool of the sampling apparatus.
36. 36. The sampling pin of claim 35, wherein at least one of the second and third expanded radial portions of the pin has a width or diameter larger than that of the first expanded radial portion.
37. 37. The sampling pin of claim 35 or claim 36, wherein one of the second and third expanded radial portions of the pin has a depth greater than that of the other of the second and third expanded radial portions.
38. 38. The sampling pin of any one of claims 33 to 37, wherein the elongate body of the pin is hollow and is adapted to receive an elongate pin member, said pin member being slidably received in the hollow such that a tip portion of the pin member extends below an end of the pin, said tip portion of the pin member comprising the tip portion of the pin.
39. 39. The sampling pin of claim 38, wherein the pin member has a head portion of greater diameter than the hollow, said head portion of the pin member being adapted to be supported in a recess provided in an upper expanded radial portion of the pin.
40. 40. The sampling pin of any one of claims 33 to 39, wherein a surface area of a face of the tip portion of the pin which contacts with a growth medium is sized with respect to the weight of the pin or the pin member to exert on a surface of the growth medium a pressure that is equal to or less than a predetermined threshold pressure.
41. 41. The sampling pin of claim 40, wherein the predetermined threshold pressure is dependent on a type or characteristic of the growth medium.
42. 42. A sampling pin cartridge comprising a plurality of apertures in a tray member, said apertures arranged in said tray member in an array and each aperture adapted to receive a tip portion of a sampling pin to support said sampling pin in a manner such that said pin can be individually picked out of the cartridge by an automated tool of a biological sampling apparatus.
43. 43. A computer readable medium carrying machine readable instructions executable by a processor of a computer, said machine readable instructions for implementing in an automated sampling apparatus the steps of the methods of any one of claims ito 20.