阅读说明：本技术 用于自动操纵移液器的方法和系统 (Method and system for automatically manipulating pipettes ) 是由 雅各布·菲约德加尔·肖耶隆德 克里斯蒂安·卡尔森 于 2020-02-19 设计创作，主要内容包括：本发明涉及一种用于自动操纵移液器的方法和系统。该系统包括用于识别移液器的识别装置、被配置为对所述移液器执行操纵操作的机器人、以及控制单元。该控制单元被配置为从数据库获得与移液器相关的数据,并且其中,该控制单元被进一步配置为从识别装置和机器人中的一者或多者获得数据。(The present invention relates to a method and system for automatically manipulating a pipette. The system includes an identification device for identifying a pipette, a robot configured to perform a manipulation operation on the pipette, and a control unit. The control unit is configured to obtain data relating to the pipette from a database, and wherein the control unit is further configured to obtain data from one or more of the identification device and the robot.)

1. A method for automatically manipulating a pipette, the method comprising the steps of:

A. identifying pipettes using identification devices

B. Obtaining data relating to the identified pipettes from a database using a control unit

C. Performing a manipulation operation on the pipettor using a robot

And

D. obtaining data of the manipulation operation from one or more of the recognition device and the robot using the control unit.

2. A method according to claim 1, wherein the control unit is configured to process the data obtained in steps B and/or D to compare said obtained data with existing data on the database.

3. The method according to any one of claims 1 or 2, further comprising the steps of:

E. recording the data obtained in step B and/or D to the database.

4. The method of claim 3, further comprising the steps of:

F. the manipulation operation is controlled using the control unit based on the data obtained in step B, step D and/or the data recorded in step E by sending instructions to the robot.

5. The method of claim 4, wherein the control unit predicts an output from the control of the manipulation operation based on the obtained data and/or recorded data.

6. The method of claim 5, wherein the control unit controls the manipulation operation based on the prediction.

7. The method according to any one of the preceding claims, wherein the manipulation operation comprises calibration or verification of the pipette.

8. The method according to any one of the preceding claims, wherein the manipulation operation comprises repeated pipetting of the pipette.

9. A method according to any preceding claim, wherein the manipulation operation comprises a characterisation of the liquid being aspirated and/or dispensed.

10. A method according to any of the preceding claims, wherein the manipulation operation comprises a plurality of parameters, wherein at least one of the plurality of parameters of the manipulation operation is changed.

11. A system for automatically manipulating a pipette, the system comprising:

a recognition device for recognizing the pipette, a robot configured to perform a manipulation operation on the pipette, and a control unit;

wherein the control unit is configured to obtain data relating to the pipette from a database, and wherein the control unit is further configured to obtain data from one or more of the identification device and the robot.

12. The system of claim 11, wherein the control unit is further configured to process the obtained data and compare said obtained data with existing data on the database.

13. The system according to claim 11 or 12, wherein the control unit is configured to record the obtained data to the database.

14. The system according to any of claims 11 to 13, wherein the control unit is configured to control the manipulation operation based on the obtained data and/or recorded data by sending an instruction to the robot.

15. The system of claim 14, wherein the control unit predicts an output from the control of the manipulation operation based on the recorded data.

16. The system of claim 15, wherein the control unit controls the manipulation operation based on the prediction.

17. The system according to any one of claims 11 to 16, wherein the manipulation operation comprises a plurality of parameters, wherein the control unit is configured to change at least one of the plurality of parameters of the manipulation operation.

18. A system according to any of claims 14-17, wherein the system comprises sensors for measuring environmental parameters, and said control unit is configured to obtain environmental data from said sensors, and wherein the instructions sent to the robot are based on said obtained environmental data.

19. The system of any one of claims 11 to 18, wherein at least the identification device and the robot are placed in a controlled environment.

20. A computer readable medium comprising computer readable code, wherein the computer readable medium is configured to implement the method of any of claims 1 to 10.

Technical Field

The present invention relates to automated manipulation of pipettes, and more particularly to methods of and systems for automatically manipulating pipettes.

Background

Pipettes used in laboratories, such as in the pharmaceutical industry or research, experience repeated use, wear, misuse and impact during their lifetime, which may reduce their accuracy characteristics. Therefore, it is important to ensure that pipettes conform to manufacturer's specifications and regulatory standards as they are operated. For example, ensuring that the accuracy of the liquid being aspirated and dispensed is within a specified error range or uncertainty. Therefore, compliance certification testing and calibration of pipettes is a very important aspect in the life of pipettes, and most pipettes are subject to maintenance schedules including calibration and verification protocols. In addition to the accuracy characteristics, another very important issue is the strong interest in understanding the development and impact parameters associated with the development of these characteristics, as well as the ability to assess and take action on the knowledge and impact of the parameters while manipulating the pipette.

For example, testing and calibration must be performed periodically, and thus pipettes are typically shut down from production and sent out of the laboratory when calibration and certification is required. This may be, for example, after a certain frequency of use, a certain number of operators have used the pipette, dispensed a certain liquid, or after the pipette has been damaged or dropped on the ground causing the pipette user and owner to question the performance of the pipette. In performing these tests and calibrations, several parameters are tested and certain test conditions must be observed in performing these tests and calibrations. Testing and calibration is typically performed by an authorized facility (such as a test station or calibration facility) or a trained operator in a laboratory.

One such challenge is that pipettes sent out for certification or calibration suffer from considerable downtime. Thus, an owner/laboratory may need to own multiple sets of pipettes, or in some cases lack many pipettes during a pipette departure. When pipettes are moved into and out of a laboratory, they often require a treatment, such as sterilization or autoclaving, which is another complicated and cumbersome step. The longer the interval between verifications or calibrations, the greater the risk of testing using an inaccurate or faulty pipette, thereby rendering the large number of tests and experiments performed useless.

Furthermore, one challenge is that pipette maneuvers, which themselves will affect their performance, change throughout their stroke and throughout their life.

Pipette handling, in particular calibration and testing of pipettes, is mostly performed manually by a human operator. A human operator who performs the manipulation works in an uncomfortable position, and many parts of the body are subjected to load due to repeated moving and static works in the manipulation operation. This is a lengthy and repetitive process which in turn also involves many sources of error. Each human operator handling a pipette will introduce a different source of error because each operator has a different way to handle the pipette. This also makes it difficult to keep track of changes in pipette manipulation and accuracy of tracking.

WO 2005/085775 discloses a pipette verification device which may be mounted on an existing pipette or may be integrated therein. The pipette verification device includes a sensor, allowing data required for pipette verification to be provided, including data regarding the performance of a human operator who needs to identify himself as part of a process. Even though it is briefly suggested that the piston may be driven by a motor and may thereby relieve some repetitive stress on the operator, as disclosed, the entire validation process still involves a human operator manipulating the pipette.

Another challenge when manipulating pipettes is keeping track of and documenting pipette performance. Some administrative systems for keeping track of pipette sets already exist. An example of a purely administrative system for pipettors is disclosed in WO 2017/173380a 1. As a purely administrative system, WO 2017/173380a1 does not mention any manipulation of the pipette.

Disclosure of Invention

In this context, it is an object of the present invention to minimize or eliminate the source of error when handling pipettes. It is another object of the present invention to improve the consistency of handling pipettes. Another object is to reduce downtime of a pipette for the owner by providing more efficient and flexible manipulation of the pipette. Another object is thus to minimize manual operations related to manipulation of the pipette. Another object is to achieve this object in a more automated manner, reducing the physical burden on a human operator who manually performs pipette manipulations. Furthermore, the aim is to minimize the uncertainty associated with manual manipulation. Another object is to be able to characterize pipettes, their performance in relation to manipulation or operation and in relation to automatic manipulation and operation, and to document these relationships. A more accurate tracking and documentation of the manipulation of the pipette and a detection of a source of error or a development of performance in connection with the manipulation of the pipette can thereby be achieved, while the manipulations performed are also an object of the present invention. The invention may therefore be useful in understanding influencing parameters and the development of these influencing parameters that will contribute to the accuracy characteristics described above. The invention may also enable the recording of influencing parameters, whether one or more parameters are recorded together or individually.

According to a first aspect of the present invention, these and other objects may be achieved by a method for automatically manipulating a pipette, wherein the method comprises the steps of:

A. identifying pipettes using identification devices

B. Obtaining data relating to the identified pipettes from a database using a control unit

C. Performing a manipulation operation on the pipettor using a robot

And

D. obtaining data of the manipulation operation from one or more of the recognition device and the robot using the control unit.

Automatic manipulation is to be understood as pipette manipulation with substantially no manual manipulation or substantially no manual influence on the manipulation of the pipette and the performance characteristics described.

The pipettor may be any type of piston operated volumetric device. This includes, for example, single channel piston pipettes, such as positive displacement pipettes or direct displacement pipettes, air displacement pipettes, multichannel piston pipettes, micropipettes or bulk pipettes. The pipettes are preferably hand-held pipettes held and operated by a robot during manipulation operations, but may alternatively be pipettes integrated in, for example, a liquid manipulation system (e.g., an automated liquid manipulation system including a pipettor forming portion, e.g., a robot or robotic arm), or automated pipettes. The pipette may also be a piston-free pipette, such as a pipettor.

By having a method for automatically manipulating pipettes, wherein data from manipulation operations is obtained, improved consistency of pipette manipulation may be achieved. The obtained data also allows to document the performance of the manipulated pipettors in an active manner when performing manipulations and may thus allow to characterize each manipulated pipettor in a more accurate and personalized manner compared to the management system disclosed in, for example, WO 2017/173380a 1.

Another advantage of using a robot for the manipulation operation is that manipulation of the pipettes may be performed in a more efficient and faster manner. Another object is to reduce downtime of a pipette for the owner by providing more efficient and flexible manipulation of the pipette. Another object is to minimize manual operations and manipulations associated with pipette manipulations. The manipulation according to the invention can be performed at all times, since it is automated and requires substantially no human operator. For example, this may be the manipulation of the pipette by the robot at night, when the pipette is not in use, such as for a hand-held pipette used by a human worker during daytime work hours. Thus, a group of pipettes may undergo different manipulation operations, such as part of a periodic maintenance while the pipettes are empty, so that downtime of the pipettes during working hours may be reduced. Another advantage of achieving this in a more automated manner is that the physical burden on the human operator performing these repetitive manual manipulation operations is reduced. Furthermore, two people performing the same manipulation operation on the same pipette may not be performed in a uniform manner. The resulting manipulation operations will be different for each different person, each different pipette, and each different manipulation operation performed. Even for the same person manipulating the same pipette from one manipulation to another. For example, the performance of a person may change during the day due to fatigue or the like, but it is considered that even a slight change such as a heart rhythm affects the manipulation. This may be recorded, processed and/or it may be used to control the manipulation operations and different and/or varying manipulations may even be avoided by the method according to the invention. That is, the robot will perform the manipulation in a consistent and accurate manner, allowing each repeated pipetting action to be performed in exactly the same manner during the manipulation operation.

Using this approach, tracking of changes in pipette manipulation and changes in tracking accuracy can be done actively rather than passively, and thus establishment of a pipette network rather than a pipette collection can be achieved. A pipette network is understood as a relationship between pipettes, wherein each pipette can be individually manipulated and tracked, but can also be manipulated and tracked in a manner that can document it according to its influence on other pipettes, so that the performance of the pipette network is better than the sum of the pipettes if the pipettes are individually manipulated and tracked.

However, the robot may also be actively controlled to make deviations in order to know which individual parameters influence pipette performance development over time, for example to change the heating or acceleration of the pipettes in a controlled manner.

The control of the manipulation operations on the basis of the relationship parameters between the individual pipettors makes it possible to establish a pipette network using the method according to the invention.

Further, a human operator may not be required, and if one is required, the operator does not have to be qualified or certified for manipulating the pipette. In some embodiments, one of the only tasks for the operator may be, for example, loading a pipette onto the robot. However, in other embodiments, the robot may be configured to automatically load pipettes. This leaves the operator, especially a qualified operator, more time to perform other tasks. Another advantage is that more pipettes can be handled at one time, compared to a human operator who can only handle one pipette at a time. This in turn may also be a cheaper and more efficient way of handling pipettes.

The identification of the pipettor is done by an identification device. Each pipette preferably has a unique ID that the identification means can identify and/or verify. Preferably, the pipette has an information carrier comprising the ID of the pipette, which information carrier may preferably not be removable and which may be printed on or engraved in the pipette. The information carrier may be, for example, a bar code, a serial number, an RFID (radio frequency identification ID) code, a QR code, or any type of chip carrying ID information. The identification means may be placed on a gripper of the robot or may be separate from the robot and is preferably configured to identify any type of pipette and any type of information carrier. In some embodiments, the identification device may alternatively be configured to identify a specific type of pipette or a specific type of information carrier, such that it may be of simpler construction or design, or such that it may allow the system to be mobile or contained in a controlled or categorized environment. The identification device should preferably have at least one element for identifying the pipette corresponding to the information carrier type of the pipette. For example, the camera may be capable of recognizing a barcode, serial number, or QR code, while the RFID reader may be capable of recognizing an RFID tag. An advantage of identifying a pipette by means of the identification means is that it can be performed in a faster and more accurate manner than a human operator performs pipette identification. A further advantage is that the identification means can also read and identify information carriers which are not readable by humans, such as QR codes, RFID tags or information carriers located in inaccessible locations, or access information about pipettes which may have been displayed to the operator during the identification phase.

By identifying a pipette, one pipette may be distinguished from another pipette, so that data relating to the identified pipette may be obtained from a database using the control unit. The control unit may be operatively connected to different elements according to the invention, such as a recognition device, a robot or any other element according to the invention. The control unit may be wirelessly connected to these different elements. Furthermore, the control unit may be connected to an external network, wherein the network may be for example an in-building network of the pipette owner or a global network such as the internet. The control unit may thus be located beside or at a distance from the other elements.

The control unit may be configured to have access to pre-stored and/or pre-programmed software and algorithms to obtain data and perform manipulation operations stored on the database or an alternative database. The database may be mirrored, for example, where the pipette network is extended. Alternatively, the control unit may receive input, e.g. from an operator, to take over the automatic manipulation, e.g. if an error in the automatic manipulation is detected. This may be done remotely, for example, from an operator's interface. The control unit may also be configured to send outputs (e.g., control signals) to these various elements. The obtained data may be data stored in advance on a data storage unit such as the database. Alternatively, the obtained data may be received at the control unit, for example from a recognition device, a robot, a sensor or a camera.

The control unit can access a database to obtain data related to the pipette.

This data may be historical data, such as historical usage of the identified pipettor, a laboratory in which the pipettor was used, activities for which the pipettor was used, a user or operator who used the pipettor, or maintenance history of the pipettor, such as whether components were replaced during the lifetime of the pipettor or when calibrating or verifying the pipettor. The data may also be information about the pipette, such as the manufacturer, model, or which group of pipettes the pipette belongs to, or it may be data about performance predictions related to the pipettes and/or pipette network. By obtaining data related to the pipette, information such as historical data related to the pipette may be accessible prior to performing a manipulation operation on the pipette. A human operator manipulating a pipette does not necessarily have access to such information by identifying the pipette. Even if a human operator could access such data, it would be more cumbersome and would take more time to obtain the data, and he would not be able to process the data as quickly. By obtaining data for a pipette during the identification phase, data obtained from a manipulation operation may be actively compared and matched against existing historical data from the identified pipette or from any other pipettes recorded on the database, rather than passively obtaining and comparing data after the manipulation operation is performed. When the data is obtained and compared only after the manipulation operations are performed, as is done today by human operators or management systems, it is not possible to consider the performance before and during the manipulation operations are performed, but only afterwards. Thus, a large amount of information is lost and never associated with a particular parameter or performance.

When a pipette has been identified, there may be a variable amount of data associated with the pipette to be obtained, for example, depending on whether the pipette has been previously identified. Data relating to a pipette may be obtained even if the pipette is identified for the first time. This may be, for example, stored data associated with that particular type of pipette, historical data from other pipettes from the same manufacturer, data from any other pipettes recorded on a database, or general specifications associated with pipettes such as size, volume range, or user.

The data related to the identified pipettes may be data from previous manipulation operations performed on the same pipettes, but may also be data from the same type of pipettes, from pipettes used in the same laboratory or department or from pipettes used by the same operator, robot, a particular set of parameters, predictions, manipulation operations, etc.

The manipulation operation performed by the robot on the pipette may be, for example, one or more of the following operations:

moving the pipette from one position to another, replacing the disposable tip of the pipette, depressing the plunger of the pipette, releasing the plunger, filling the pipette with the test liquid by depressing and releasing the plunger so that the pipette sucks in the liquid, emptying the test liquid of the pipette by depressing and releasing the plunger so that the pipette dispenses the liquid, immersing the tip in the test liquid, waiting for a period of time, accelerating in a given manner, vibrating, removing the tip from the test liquid, contacting or wiping the tip against the wall of the container containing the test liquid, removing the tip from the wall of the container, weighing the sucked or dispensed liquid. The manipulation operations performed by the robot may include one, more, some, most, substantially all, and/or all of the manipulation operations described above. The same manipulation operations may be repeated several times one after another, or with other manipulation operations interposed. An example of a manipulation operation that is repeated several times one after the other may be wetting a pipette tip several times, for example by dipping the tip.

The first fill of a pipette may be to wet the tip of the pipette.

Manipulation operations on a pipette may also include operations performed in connection with the pipette, such as identification of the pipette, adjustment of it, its environment, measurement of its characteristics (such as weight or temperature), documentation of these characteristics, or transportation thereof.

The manipulation operations performed by the robot may comprise a single operation or may comprise several operations, for example forming a group or set of manipulation operations. The set of operations may be a desired set of operations, a sequence or series of operations, for example corresponding to a calibration test, a compliance test, a verification test or a pipetting operation. The manipulation operations may also include a set of customized manipulation operations. The manipulation operations may be separated by different time intervals, for example.

In some embodiments, the manipulation operation of step C may be performed before step a, i.e. step C is performed before step a. This may be the case, for example: pipettes are grasped or mounted and moved towards the identification means for identification, or handling requirements describe situations where this would be advantageous. The manipulation operations may thus comprise operations performed before, simultaneously with and after the verification step. Step C may thus be performed before step a and repeated after step B. As mentioned above, the identification of a pipette may thus be part of the manipulation operation. Thus, the skilled person will understand that not all manipulation operations need to be performed by the robot. Instead, one, more, some, most, substantially all of the manipulation operations may also be performed by other elements than the robot according to the invention. Thus, a manipulation operation or set of manipulation operations should not be limited to being performed by only a robot, and may be performed by a combination of robots and other elements in some embodiments, for example, to meet manipulation needs or particular performance or test requirements.

The steps of the method may be repeated, for example, to manipulate, calibrate or validate pipettes multiple times, to manipulate, calibrate or validate a group of pipettes, or if manipulation, validation or calibration of a pipette was not initially performed correctly. The steps of the method are preferably continuous, but may alternatively be in another order.

The data obtained for the manipulation operation may be any information related to, for example, any of the above-described operations. This data may be understood as data from the manipulation operation, but may alternatively be understood as data relating to the manipulation operation itself or data relating to the output of the manipulation operation. This may be, for example, a registration of the time taken for the manipulation operation, a tracking of the movement of the pipette, a load applied to the plunger of the pipette, or a weighing of the liquid aspirated or dispensed.

Data from manipulation operations may be obtained at any time, which may be, for example, before manipulation operations, while manipulation operations are being performed, or after manipulation operations. The acquisition of data may also be indicated as being acquired in real time or in situ.

By obtaining data from the manipulation operations, such as verification or calibration of pipettes, may be adapted, adjusted, and monitored. Such adaptation, adjustment and monitoring of the manipulation of the pipettor may be performed actively, for example, while the manipulation is being performed or after the manipulation. This has the further advantage that handling pipettes can be done in a more consistent and uniform manner than known handling methods, such as those used in manual calibration, validation or pipetting. Furthermore, it is advantageous that the manipulation of the pipette can be adjusted during the manipulation and the adjustment is recorded and the effect is documented, so that for example complex manipulation operations are not susceptible to external changes, such as temperature changes, unexpected gas flows, equipment/consumable failures or processes being interrupted. The data obtained can thus always give feedback on the steering operation. By obtaining historical data prior to performing a manipulation operation and real-time data as the manipulation operation is performed, performance of the pipette may be consistently characterized and documented. This allows real-time documentation and real-time tracking of pipette performance. Furthermore, the manipulation can be actively improved and can be done in a more accurate way.

The control unit may obtain data from the steering operation from any element. This may be done, for example, by any part of the robot, the identification means or any other separate element, such as a sensor or detector.

The manipulation operations must be performed at least partially by the robot. The robot may be adapted to perform any manipulation operation (such as the examples of manipulation operations described above), and may be capable of manipulating any type of pipette. The robot may, for example, be adapted to move the pipette from one location to another, change a disposable tip of the pipette, depress a plunger of the pipette, release the plunger, fill the pipette with a test liquid by depressing and releasing the plunger such that the pipette draws in liquid, empty the test liquid of the pipette by depressing and releasing the plunger such that the pipette dispenses liquid, immerse the tip in the test liquid, wait a period of time, remove the tip from the test liquid, contact or wipe the tip on a wall of the container containing the test liquid, weigh the drawn-in or dispensed liquid, or remove the tip from the wall of the container. The robot may be made up of one or more elements. The identification means may be comprised in the robot or may alternatively be a physically separate element from the robot. The robot may, for example, include one or more pipette manipulation interfaces, such as arms, motors, pistons, grippers, wheels, actuators, or sensors. By identifying the pipettes to be manipulated, information related to the pipettes is collected, and the control unit may thereby be able to send instructions to the robot, for example adapting the type or size of the hand grip to the size of the identified pipettes, allowing manipulation of any type or size of pipettes. The robot may include one or more grippers adapted for pipettes of different size ranges or types. The robot may have been pre-fitted with one or more grippers or may alternatively have the possibility of having a replaceable gripper if only one gripper can be fitted at a time. The gripper of the robot may be, for example, a fingered gripper, a flexible finger, a spherical gripper (such as a flexible ball filled with particles), or a custom-made gripper (such as a 3d printed gripper) adapted for a particular type of pipette, for example. So that the robot may be adapted to make the pipette easy to remove and mount on the gripper. In some embodiments, the identification means may be included or embedded in the hand grip. The grip may also be referred to as a holder or hand, for example. The robot may include a temperature-changing element, for example, positioned in relation to the hand grip or adjacent environment or element, such that the temperature to which the pipette is exposed when held by the hand grip may be changed. Depending on the application, the temperature-changing element may heat or cool the pipette. For example, the hand grip may have a heating element that may heat the pipette while holding the pipette to simulate the warmth of the hands of a person holding the pipette, thereby simulating the effects of such manual manipulation of the pipette. The temperature-changing element can be, for example, a thermoelectric element, such as a peltier element, which can heat or cool the pipette. For example, it may be desirable to stabilize the temperature of a pipette after the pipette is used by a human operator. By having a temperature-changing element, it is possible to simulate temperature changes, for example, due to manual manipulation of a pipette within a manually manipulated time interval, and thereby isolate individual parameter changes of the manipulation operation, in this case temperature. The gripper for the pipettor may be arranged such that the pipettor in the mounted condition is supported in a manner such that the pipettor is substantially movable in one direction only, and substantially immovable in any direction in the manipulated condition and thereby locked in place. This may be accomplished by clipping the pipette onto the grip, for example by attaching a hinged or rotatable upper portion of the grip around the pipette or by securing the pipette in the grip using a locking mechanism. The locking mechanism may be electronically operated, for example by magnetic or gravity, whereby the pipette may be in a state mounted on the hand grip. The installation may be done manually by an operator, but may also be done automatically by a robot.

The gripper may be arranged such that the pipette in the mounted condition is supported in a manner such that one axis of movement is substantially fixed and the pipette is movable in substantially all but one direction and, if desired, is substantially unable to move in any direction under manipulation operations and is thereby locked in place. The pipette can thus be mounted in a "loose" state to the gripper and, if desired, in a "fixed" manner. This may be done, for example, by supporting the pipette in the mounted state on a grip at three points or areas of the pipette, wherein the first and second support points or areas may be realized using a guide of an upper portion of the grip guiding the pipette in place, and the third support point or area may be realized by a curved portion of a fixed lower portion of the grip into which the pipette is pressed by an actuating mechanism, the curved portion substantially following the shape of the pipette. The third support point or region provides support, for example, at a point or region closer to the tip of the pipette than the first and second support points or regions, thereby achieving stable support of the pipette.

The locked state of the pipette may be achieved by arranging the upper portion of the grip such that the hinged or rotatable attachment allows the upper portion to cover the pipette and push it into position. The grip may include, for example, an activation mechanism for actuating a plunger of the pipette, which may be, for example, a mechanical plunger or an electronic plunger mechanism such as a button. The activation mechanism may be included in the upper portion of the grip or may be provided as a separate part. In the locked state, the activation mechanism should preferably be in a position that will activate a plunger of, for example, a pipette. Alternatively, the activation mechanism may also be in a position that will activate the plunger of the pipette in, for example, a "loose" mounted state of the pipette. A locked state of the pipette may also be achieved when the activation mechanism activates the pipette and thereby pushes it into position. This may allow for stable positioning under handling conditions for different pipettes of the same or different models. By holding the pipettor in a stable operating position, the position of the pipettor can be kept constant and thus also known to be relevant at all times. Thereby, the accuracy of the manipulation can be improved.

The hand grip may, for example, be designed to support the pipette in a manner similar to a human hand. Many pipettes are ergonomic and are designed to fit in the human hand so that they can remain stationary when manipulated. Thus, the gripper may support the pipette, for example at an ergonomic shoulder of the pipette. The robot may thus take advantage of the ergonomic design of the pipette, for example when pressure is applied on the plunger and the pipette is supported at a specific point (e.g. its shoulder), whereby the pipette may be held in a locked position.

The activation mechanism on the hand grip may be designed in a manner such that the force, speed and precision of the activation is similar to that of a human or a group of humans (if human or not at all). This may be accomplished by allowing the gripper to flex when the pipette is activated. For example, flexing may be achieved by a hinge on the grip, by providing the grip with a different resilient material (such as steel, aluminum, plastic, or rubber) that may be capable of bending or moving, or by using a non-mechanical activation mechanism component (such as a magnetic drive component).

The grip may preferably be provided without any sharp edges. This may be achieved, for example, by using plastic parts, organically shaped design features, and removing sharp edges of the parts during assembly. Furthermore, the hand grip may preferably be designed using light weight materials and components, such as aluminum or plastic, which may not be very heavy. This may for example ensure safety and minimize the risk of damaging the environment (such as an operator), which is a major problem associated with the handling of pipettes.

The gripper may have an identification, such as a non-removable unique serial number for identifying the gripper, which may allow compliance with safety-related legal and industry-specific requirements, such as risk assessment or guidelines of the mechanical industry, traceability, e.g. asset management. This may be achieved by engraving the logo or by integrating it into the grip element. The ID may be, for example, physical or electronic.

The gripper may be configured in a manner such that no cables (such as external cables) are visible, for example, along the exterior of the robot or in the operator workspace. This can improve operator safety and minimize cleaning requirements, which may be statutory requirements or requirements to obtain operational clearance in a controlled or classified environment. In some embodiments, only one cable may be present and exit the robot and/or the gripper. This may be accomplished by wiring the robot and the gripper through the interior of the robot and gripper, or by using components that are wireless or operate independently of power.

The gripping surface may be configured to allow easy and effective cleaning, which may be a requirement for operation in a controlled or sorted environment. This may be achieved by a coating of substantially all or part of the surface of the grip, for example with a lacquer which may contain disinfecting properties or may contain surface reaction properties, such that an indication such as a colour shift or other indication occurs at different pH levels when the surface is exposed.

The hand grip may be configured such that the activation mechanism is unlikely to injure an operator or other human interacting with the hand grip. This can be achieved by using components that cannot achieve the necessary force, by shielding components or moving parts with covers that can be physical or electronic, or by limiting the performance of the components so that they operate under forces that do not cause harm. It may also be achieved by establishing a security system as part of the gripper or control unit, which may be a security key or barrier required for operating the system.

The hand grip may be constructed such that it can be exchanged for another hand grip in a quick manner. This may be less than 5 minutes, less than 3 minutes, less than 2 minutes, less than 1 minute, or less than 30 seconds. This may be achieved by using a click system, a threadless connection, or a wirelessly operated component.

The grip may be configured such that the pipette may be exchanged for another pipette in less than 5 seconds. This may be accomplished by using a threadless connection or a pipette mounting system that functions with gravity or magnetic forces.

The grip may be configured such that the pipette is held at an angle of between 0 ° and 90 °, preferably between 5 ° and 50 °, more preferably between 10 ° and 30 °, more preferably between 15 ° and 25 ° and most preferably 20 °. The hand grip may be pivoted to a minimum of 0 degrees to simulate human operation and meet manufacturer recommendations for operating pipettes. This can be achieved using a robot with at least 4 axes.

The gripper may be configured to be pivotable about the end of the pipette tip when performing manipulation operations on the pipette, for example to comply with requirements of the calibration standard ISO8655 for manipulation operations, wherein the pipette tip may have to contact the container to avoid unintentional liquid transfer while optimizing the repetitive accuracy of the pipette manipulation operations. This may be achieved, for example, using a robot with non-fixed reference points for special coordinates, such as programmable TCP points where the gripper is mounted.

The hand grip may be configured to allow easy access into confined spaces such as laboratory equipment or scales or weights supporting pipettes. This may allow for a more optimal way of manipulating a pipette than a human may comfortably or physically manipulate to reach the same type of confined space, while also maintaining accurate manipulation. This may be achieved by employing a mounting position for the pipette (e.g. 90 degrees from a position that may be used by a human being) which typically must hold the pipette so that the front of the pipette faces in a direction perpendicular to the direction that the human is facing, whereas when mounted in the hand grip in this manner, the pipette front may face forward.

The hand grip may be configured so that the liquid wand does not fall off in the event of a power failure, for example without damaging any equipment, the surrounding environment or injuring the operator. This may be accomplished by mounting the pipette in a manner that is not power dependent and/or in a manner that prevents the robot from moving the gripper to a position where the pipette may be detached from mounting.

The robot may comprise a local control unit operatively connected to the control unit, whereby the robot may be controlled by the control unit by sending instructions to the local control unit. The control unit may thus be located remotely from the robot. The robot may also comprise a local storage unit or database, e.g. so that data from the manipulation operations performed by the robot may be stored even if the connection between the control unit and the robot is interrupted. The control unit may then obtain the data stored on the local storage unit or database when the connection is re-established. The term "robot" may be understood as a device for performing tasks or operations in an autonomous manner, in particular pipette displacement and/or pipette actuation tasks. The robot may be configured to perform at least one manipulation operation. The robot may be configured to move in one, two, or three dimensions and is, for example, a single axis robot, a two axis robot, a three axis robot, a four axis robot, a five axis robot, or a six axis robot. The robot may also comprise several sub-robots of the same or different kind. Thus, the robot should not be limited to a single robotized element, but may include one or more robotized elements as well as one or more non-robotized elements.

In some embodiments, the control unit is configured to process the data obtained in steps B and/or D, so as to compare said obtained data with existing data on the database.

In some embodiments, the method further comprises the steps of:

E. recording the data obtained in step B and/or D to a database.

By recording the data obtained, it may be possible to have a pipette manipulation history recorded, for example, on a database. This further allows for the creation of a database with historical data of manipulated pipettes and data obtained while performing manipulation operations. This recorded data can then be compared and matched against the newly acquired and recorded data. This may be done before, simultaneously with, and/or after performing manipulation operations, allowing for comparison, characterization, and documentation of pipette manipulation and pipette performance based on different parameters. This may be, for example, a comparison, characterization and documentation of manipulation operations at different times over the life of the same pipette, or a comparison, characterization and documentation of manipulation operations of two or more different pipettes, where the pipettes may, for example, have the same or different manufacturer or maintenance histories, the same or different uses, such as different laboratories, for different liquids, or for use by different departments, teams or users. Further, a particular operator, operator team, method of manipulation, or manipulation operation may be characterized, and the impact on pipette performance may be defined, reported, and addressed. The owner of a pipette may establish condition-based maintenance on his pipette, and he may thereby translate his pipette management to include a network of pipettes, rather than a collection of pipettes, providing a better overview and a broader assessment of the handling and performance of his pipettes.

These comparisons may allow, for example, determining or correlating which one or more parameters may be the cause or source of error, such as a deviation in the accuracy of the pipette or any other deviation from normal performance of the pipette. The reasons may be, for example, that a pipette is more deteriorated than other pipettes due to the use of a particular liquid, that pipettes from a particular manufacturer are more or less tolerant, for example, to use multiple times before service or maintenance, that the size of the pipette, or that a particular department, team or user wears out the pipette faster than other pipettes.

Alternatively, recording may be referred to as logging down the obtained data.

Another advantage is that it is possible to determine how a pipette should be manipulated before, at the same time as, and after a manipulation operation is performed on the pipette. This may allow, for example, determining from one or more of the above parameters, for example, at what frequency the pipette should be calibrated or verified to predict manipulation and response to manipulation, and adjusting the manipulation of the pipette based on the obtained data. The recorded data may also be used to assess the quality of previous or future experiments performed by any given pipette.

In some embodiments, the method further comprises the steps of:

F. the manipulation operation is controlled using the control unit based on the data obtained in step B, step D and/or the data recorded in step E by sending an instruction to the robot.

The control unit may for example send instructions to the robot to re-perform the manipulation operation, for example because the obtained data does not match historical data on the database, or because there is an abnormal change compared to an approved range of parameters or performance known for a particular manipulation operation or a particular pipette. It may thereby be possible to assess whether a given manipulation operation is performed correctly based on historical data obtained in connection with the pipette or based on recorded real-time data (e.g. the pipette does not require further calibration or verification, or the pipette is defective or damaged). The control unit may thus send instructions to the robot to, for example, stop a manipulation operation, change parameters in one or more manipulation operations, and in some cases stop a manipulation operation. The database may include historical data relating to previously stored similar situations in which similar abnormal changes in parameters or performance of manipulation operations have been recorded. The control unit may thus be configured to adjust the manipulation operation, for example based on a comparison of the obtained data with historical data stored on a database.

The control is preferably done in an automated manner, but may also be done by an operator (e.g. if remote control is performed by a user).

In some embodiments, the control unit predicts the output from the control of the manipulation operation based on the obtained and/or recorded data.

By having a database with the recorded pipette performance, together with real-time data obtained from the manipulation operations, it is possible to predict, for example, the control of a manipulation operation, the result of that manipulation operation, or the next manipulation operation. The impact of a given manipulation operation on other manipulation operations in a pipette network may also be predicted, and thus a given manipulation operation may result in an improved performance of another manipulation operation in the network. This predictive data may be stored on a database, for example, as virtually generated data for a pipette. Virtual data is understood to be data generated for a pipette, but not necessarily data from manipulation operations occurring in reality. The output may be virtually simulated based on existing data and/or virtually generated data stored on the database. This virtual data can then be combined with historical data to estimate and predict the adjustment of the control of the steering operation and its results.

Another example may be to perform a known specific manipulation operation to challenge a specific type of pipette, or that a current pipette is close to service and/or maintenance in use or time, to perform a specific manipulation operation and/or to control a manipulation operation in a specific way in order to find out in a faster way, for example, whether the pipette is not in compliance or deviates from a known or predicted performance. The adjustment of the actuation can be, for example, a compensation of performance deviations of the pipette. This adjustment may be made based on predictions made from, for example, virtual data, historical data, real-time data, or from a combination of the foregoing. Furthermore, a prediction may be made for the pipette that was first identified and/or manipulated.

In some embodiments, the control unit controls the manipulation operation based on the prediction.

In some embodiments, the manipulation operation includes calibration or verification of the pipette.

The phrase "calibration of a pipette" may be understood as meaning that the pipette is to be subjected to a conventional calibration or test, such as a compliance test. This may be, for example, a compliance test according to the weight test method in ISO 8655-6, a manufacturer specified test method, an owner's own compliance test or calibration routine, or a custom calibration or test method. However, the method should not be limited to a specific calibration or compliance test, but may also be a validation of the pipette. Verification should not generally be as stringent as certified testing or calibration methods. Verification may be performed as an additional check in addition to a calibration or test routine. Verification may, for example, involve fewer or different steps to be performed, e.g., making verification faster or more cost effective than calibration or compliance testing.

By having a method for automatically manipulating a pipette by a robot, wherein the manipulation operation comprises calibration or verification of the pipette, an improved consistency of calibration and testing of the pipette may be achieved.

Another advantage is that calibration or verification can be performed in a more efficient and faster manner. Another object is to reduce pipette downtime for the owner by providing more efficient and flexible pipette calibration and validation. Another object is to minimize manual operations related to pipette calibration and verification. Another object is to achieve this in a way that is more automated, thereby reducing the physical burden on human operators who manually perform calibrations and tests that may be tedious, unpleasant and repetitive.

Typically, calibration testing, compliance testing or validation of a pipette includes ensuring that the accuracy of the volume of liquid aspirated and dispensed by the pipette is within a specified error range or uncertainty and documenting it. This may be the test volume of the pipette, the nominal volume, the consistency or accuracy of the pipette. Calibration and validation of a pipette may constitute one, more, some, most, substantially all, and/or all of the manipulation operations.

In some embodiments, the manipulation operation comprises repeated pipetting of the pipettor.

Some examples of repeated pipetting steps for pipettes include: filling the pipette with the test liquid by depressing and releasing the plunger so that the pipette draws in liquid, emptying the pipette of the test liquid by depressing and releasing the plunger so that the pipette dispenses liquid, wiping the tip against the wall of the container to dispense any test liquid that may remain from the tip. This is preferably done according to an explicit procedure and is preferably traceable and dockable.

In some embodiments, the manipulation operation includes characterizing the aspirated and/or dispensed liquid.

The characterization of the liquid sucked and/or dispensed may for example be a weighing of the liquid dispensed. Weighing may be accomplished by any weighing method. Preferred weighing methods may include gravimetric weighing or photometric weighing. The liquid may also be characterized by measuring the viscosity of the liquid, the electrical conductivity properties, its molecular properties obtained via nanocrystals and subsequent spectroscopic analysis, or by any other measuring instrument intended to characterize the liquid (e.g. by interacting electronically or physically with an external measuring device, such as a spectrophotometer measurement).

In some embodiments, the manipulation operation comprises a plurality of parameters, wherein at least one of the plurality of parameters of the manipulation operation is changed. By varying at least one of the plurality of parameters of the manipulation operation, one or more parameters of the manipulation operation may be isolated while keeping all other parameters constant. By isolating one or more parameters, one or more parameters may be individually tested without being affected by other parameters that change during the manipulation operation. As previously mentioned, the robot may for example comprise a temperature changing element, whereby the parameter that can be changed is the temperature to which the pipette is exposed. Other parameters that may be changed include, for example: a displacement speed of the robot, a motion pattern of the robot, a vibration pattern when manipulating the pipette, a force and/or pressure speed exerted on a plunger of the pipette. Thereby, it is possible to simulate an average human operator under a few individual parameters by varying said parameters based on imported data relating to a plurality of human operators. A pipette may also be manipulated in a manner that simulates a particular human operator, a group of operators, or according to predictions related to the accuracy of performance. This may allow the impact of various parameters on the performance of a given pipette to be estimated such that a given person or a given pipette is interchangeable in a given set of pipettes, thereby establishing a pipette network.

According to a second aspect, the present invention relates to a system for automatically manipulating a pipette. The system includes an identification device for identifying a pipette, a robot configured to perform a manipulation operation on the pipette, and a control unit; wherein the control unit is configured to obtain data relating to the pipette from a database, and wherein the control unit is further configured to obtain data from one or more of the identification device and the robot.

In some embodiments, the control unit is further configured to process the obtained data and compare said obtained data with existing data on a database.

In some embodiments, the control unit is configured to record the obtained data to a database.

In some embodiments, the control unit is configured to control the manipulation operation based on the obtained and/or recorded data by sending instructions to the robot.

In some embodiments, the control unit predicts an output from the control of the manipulation operation based on the recorded data.

In some embodiments, the control unit adjusts the manipulation operations performed by the robot based on the prediction.

In some embodiments, the manipulation operation comprises a plurality of parameters, wherein at least one of the plurality of parameters, wherein the control unit is configured to change at least one of the plurality of parameters of the manipulation operation.

In some embodiments, the system comprises a sensor for measuring an environmental parameter, and said control unit is configured to obtain environmental data from said sensor, and wherein the instructions sent to the robot are based on said obtained environmental data.

The system is thus able to adjust the manipulation of the pipettor based on the obtained environmental data, predict the outcome of or output of control over the manipulation operation, and document the performance of the pipettor. The environmental data may be temperature, barometric pressure, humidity, air flow, gas concentration, such as CO₂(carbon dioxide) concentration, etc.

In some embodiments, at least the recognition device and the robot are placed in a controlled environment.

The controlled environment may preferably be substantially airtight to air, light, vibrations, such that the environment may be isolated and completely sealed from the surroundings of the environment. The controlled environment may, for example, comprise a clean room facility, enclosed container, box, or room. The controlled environment may also be able to fit the entire system. This may for example allow the system to be mobile, transportable and movable as one unit without the need to disassemble the system components and without the need to have space for placing the system and to be able to adjust its environment. This also provides the possibility of remotely controlling or monitoring the system.

According to a third aspect, the invention relates to a computer readable medium comprising computer readable code, wherein the computer readable medium is configured to implement the method according to the first aspect of the invention.