The invention is in the field of micropipettes. In particular, the invention is related to a micropipette, a replacement part for a micropipette or a kit of parts comprising an add-on device for a micropipette. The invention is further directed to a method to determine the position of a plunger of a micropipette.

Micropipettes are widely used in laboratories to accurately measure and handle volumes of liquids. Typically, the exact volumes need to be carefully documented and results need to be reproducible. However, small deviations as well as human errors may inevitably occur. As there are often many steps within protocols that require accurate volumes to be transferred, these small deviations and human errors can add up, resulting in experimental uncertainty or unexpected outcomes. In order to trace back the origin of these outcomes, verify the procedure that has been carried out and minimize the uncertainty, it is necessary to document the steps that have been carried out. An accurate, objective and reliable documentation is therefore required. A conventional way for documentation is manual documentation. However, this is relatively error prone and time consuming.

In order to improve the accuracy within the laboratory environment and to minimize manually documenting data, smart devices have been implemented. These smart devices can measure and document objective data points, such as temperature, pressure, humidity levels, as well as procedural steps that have been taken. For the accurate measuring and documenting of volumes from a micropipette several solutions have been proposed as well.

A first example is provided in W02020/067900, which describes an add-on device for a micropipette for determining the rotational movement and longitudinal displacement of a micropipette plunger, such that pipetting actions can be quantified. The add-on device comprises a sensor such as a magnetometer for sensing at least one component of a magnetic field.

Another example is provided in W02006/111977, wherein a fluid volume sensor is used to detect the volume of fluid released from a fluid dispensing device and to produce an electrical signal which is stored in a data storage device. The volume sensor can comprise a light source to reflect light of a rotatable element and an optical sensor to receive the light. The rotational configuration of the rotational element can be computed by the received light patterns. This can for instance be used to determine the rotational movement of the plunger of a micropipette. Disadvantageously, no information on a longitudinal movement along the movement axis of the plunger is obtained.

A further example is provided in WO2018/141898. Herein a fluid transfer apparatus, such as a pipette comprises a user interface device comprising a motion sensor device for measuring motion data which can be stored. The motion data can for instance be related to the path of motion of the pipette.

Other options include an electronic micropipette. However, these devices are expensive and vulnerable. Additionally, electronic micropipettes are more difficult to clean and require more service due to the number of parts and their sensitivity.

It is an object of the present invention to provide a micropipette or a kit of parts comprising an add-on device for a micropipette and a method to determine the position of the plunger that overcomes at least part of the above-mentioned drawbacks. In particular the micropipette or kit of parts according to the present invention may be used to accurately determine the volume setting and plunger movement. The present inventors surprisingly found that this can be achieved by a micropipette or a kit of parts comprising a first magnetic source and at least two magnetometers. It was found that as such, magnetic background noise can be reduced. Further, it was realized that the present invention may also be used to determine pipette usage and pipette technique quality.

Figure 1 shows a schematic illustration of a conventional micropipette known in the art.

Figure 2 shows a schematic illustration of a micropipette comprising a first magnetic source, a first magnetometer and a second magnetometer.

Figure 3 shows a schematic illustration of an add-on device attached to the body of a micropipette

Figure 4 shows a schematic illustration of an add-on device attached to the finger hook of a micropipette.

Figure 5 provides a schematic overview of the electronic layout of a suitable circuit board.

Thus, in a first aspect, the present invention is directed to a micropipette comprising a first magnetic source. The micropipette further comprises a first magnetometer for sensing a magnetic field of the first magnetic source and of a second magnetic source and a second magnetometer for sensing a magnetic field of the first magnetic source and the second magnetic source. The first magnetometer is located closer to the first magnetic source than the second magnetometer.

The invention is further directed to a kit of parts comprising a first magnetic source and an add-on device for attachment to a micropipette. The add-on device comprises a first magnetometer for sensing a magnetic field of a first magnetic source and of a second magnetic source and a second magnetometer for sensing a magnetic field of the first magnetic source and the second magnetic source. The add-on device is configured such that the first magnetometer is located closer to the first magnetic source than the second magnetometer when the add-on device is attached to the micropipette.

The invention is further directed to a replacement part for a micropipette. This replacement part may suitably be used to introduce a first magnetic source to a micropipette, such as a commercially available micropipette. Accordingly, the replacement part may comprise a first magnetic source. It may also be that the first magnetic source is comprised by a micropipette of which a part is to be replaced by the replacement part.

The replacement part may additionally or alternatively comprise a first magnetometer for sensing a magnetic field of the first magnetic source and of a second magnetic source and a second magnetometer for sensing a magnetic field of the first magnetic source and the second magnetic source. Such a replacement part may be used to introduce the first and second magnetometer in a micropipette.

Another aspect of the invention relates to a method for determining the position of a plunger of the micropipette or of a micropipette comprising the replacement part or of a micropipette attached to the add-on device of the kit of parts. The method comprises sensing the magnetic field provided by the first and second magnetic sources using the first magnetometer to generate a first magnetic field data. This magnetic field data is stored in a first magnetometer data set. Similarly, the method comprises sensing the magnetic field provided by the first magnetic source and the second magnetic source using the second magnetometer to generate a second magnetic field data. This second magnetic field data is stored in a second magnetometer data set. The first and second magnetometer data sets are further processed to extrapolate the position of the plunger.

A micropipette is known in the art and is used to describe a laboratory instrument that can accurately and precisely transfer volumes of liquid (see e.g. Miller et al. The American Biology Teacher 66(4), 2004, 291- 296). It is thus a fluid handling apparatus. A schematic illustration thereof is presented in Figure 1. In this context it is used to describe a manually operated, handheld micropipette. Micropipettes (1) are available in a variety of sizes and designs, however all comprise a plunger (2), a plunger button (3), a body (herein also referred to as barrel) (4), a tip cone (6), a tip ejector button (7) and a finger hook (herein also referred to as grippy) (8). A volume display (5) may optionally be present. The tip cone (6) can be used to attach a tip, which can be easily ejected using the tip ejector button (7). The plunger (2) is positioned at least partially in the body (4), such that movement of the plunger (2) relative to the body (4) allows for a pressure difference and subsequent liquid uptake or ejection. Movement of the plunger for liquid uptake or ejection is only along the longitudinal axis of the micropipette i.e. in one dimension. The plunger (2) can be moved by using the plunger button (3). The volume setting may be adjusted e.g. by rotating the plunger, by the plunger button (3) or by another volume adjustment dial (not shown separately) to alter the volume settings, which setting can be read from the optional display (5).

The micropipette or kit of parts according to the present invention comprises a first magnetic source. This first magnetic source may be present on or in a static part of the micropipette, for instance the body or the finger hook or it may be present on or in the add-on device. Alternatively, the first magnetic source may be present on or in a moving part of the micropipette, such as the plunger or plunger button. The first magnetic source can e.g. be integrated into the plunger button. The replacement part may also comprise a first magnetic source. Accordingly, any of these static and/or moving parts of a micropipette may be a replacement part. It is preferred that the first magnetic source is in direct contact with the plunger of the micropipette. With direct contact it is herein meant that the first magnetic source moves and travels the same path as the plunger. In order to extrapolate the position of the plunger, the first magnetic source typically changes positions relative to the first and second magnetometer. The movement of the first magnetic source with respect to the magnetometers result in sensing local fluctuations of the magnetic field, that may be associated with the position and change of position of the plunger. As such, if the first magnetic source is present on a static part of the micropipette or add-on device, the first and second magnetometer may be on the moving part of the micropipette or vice versa.

Figure 2 provides an illustration of an example of a micropipette according to the present invention, said micropipette (1) comprising a first magnetic source (9), a first magnetometer (10) and a second magnetometer (11). The first magnetic source (9) is herein illustrated to be integrated in the plunger button (3), thus on a moving part. The first magnetometer (10) is located on the body (4). The second magnetometer (11) is also located on the body (4), but further away from the first magnetic source (9) than the first magnetometer (10).

The first magnetic source, first magnetometer, the second magnetometer and all further sensors and elements as described herein may be integrated in the micropipette, meaning that it is incorporated in a fixed manner in the micropipette, e.g. in its housing. Advantageously, this is aesthetically pleasing, allows favorable handling of the pipette and ensures protection of the sensors from the environment. Furthermore, the ergonomics of the micropipette are not negatively affected. However, a drawback of this approach is that existing micropipettes in laboratory environments cannot benefit for the present invention and require replacements. Given the numerous pipettes already present in the field, it is preferred to provide an add-on device that can be used to equip existing, conventional micropipettes with the first magnetometer, the second magnetometer and all further sensors and elements as described herein. The add-on device may for instance be a clip-on device that can be clipped onto the body and/or the finger hook of a micropipette. Alternatively, the add-on device can be added to the micropipette with adhesives (e.g. glue and/or Velcro™), screws or any other suitable means for attachment.

Figure 3 provides an example wherein the add-on device (12) comprises the first magnetometer (10) and the second magnetometer (11), wherein the add-on device (12) is attached to the barrel (4) of a micropipette (1). The micropipette (1) comprises the first magnetic source (9) in the plunger button (3).

Another example is illustrated in Figure 4. Herein the add-on device (12) comprises the first magnetometer (10) and the second magnetometer (11). The add-on device (12) is attached to the finger hook (8) of a micropipette (1). The micropipette (1) comprises the first magnetic source (9) in the plunger button (3).

In addition to the add-on device, the present invention provides a attachable first magnetic source that can be added to a convention micropipette, e.g. to the plunger button. Together, the add-on device and the first magnetic source can be provided as a kit of parts.

The replacement part according to the present invention may advantageously be used to introduce the first magnetic source and/or the first and second magnetometers in a micropipette. In particular, if the replacement part comprises the first and second magnetometer, it may be preferred that the first magnetometer is located closer to the first magnetic source than the second magnetometer when the replacement part is comprised by the micropipette. In cases where the replacement part comprises the first magnetic source and the first and second magnetometer, it is preferred that the first magnetometer is located closer to the first magnetic source than the second magnetometer. The micropipette comprising the replacement part may thus comprise at least a first magnetic source, a first magnetometer and a second magnetometer wherein the first magnetometer is closer to the first magnetic source than the second magnetometer. Further, if any part of the micropipette according to the present invention has been damaged, a suitable replacement part may advantageously be employed without having the need to replace the whole micropipette. Accordingly, the replacement part preferably comprises any of the static and/or movable parts of a conventional micropipette. The replacement part is thus preferably selected from the group consisting of: a plunger, a plunger button, a body, a tip cone, a tip ejector and/or a finger hook.

The first magnetic source may be a permanent magnet. A permanent magnet allows for a magnetic field to be continuously provided, such that the first and second magnetometers continuously sense a magnetic field that may be used to generate magnetic field data sets. The magnetic field should be strong enough to provide a sufficient strength for at least the first magnetometer to sense. However, depending on the first magnetic source and the location of the second magnetometer, the second magnetometer may also sense the magnetic field provided by the first magnetic source. Additionally, it is preferred that the magnetic field strength of the first magnetic source is larger than the magnetic field strength of the second magnetic source. The magnetic field strength is dependent on i.a. the volume of the magnetic source. Large magnets can be considered dangerous and are typically too heavy for the practical application of the present invention. Accordingly, it is preferred that the permanent magnet has a maximum volume of 5 cm ³ , preferably at most 3 cm ³ , such as at most 1 cm ³ .

The present inventors found that the accuracy of the first magnetometer is diminished by magnetic background noise that originates from the second magnetic source. The term second magnetic source as used herein to describe one or a collection of various magnetic sources that create a magnetic field which can be sensed by the first magnetometer, besides the first magnetic source. The second magnetic source may thus be considered as the magnetic field provided by any magnetic and/or magnetizable objects in the background. An example of magnetic background noise is the earth’s magnetic field. In a lab environment there may also be electronic devices present that provide a magnetic field that can be sensed by the first and second magnetometer. Additionally, or alternatively the micropipette or other lab materials may comprise ferromagnetic materials that can give magnetic background noise. Ferromagnetic is a well-known term to describe a property of a material that has unpaired spins. These spins can all be aligned into the same direction, resulting in a large magnetic field, or may be ordered within smaller domains. Depending on the orientation of these domains, the magnetic field of the material can be high or low. In case the domains are oriented such that no or almost no magnetic field is provided, an external magnetic source (e.g. the first magnetic source) may be used to align the domains such that the ferromagnetic material gets magnetized. Accordingly, the magnetic field of the second magnetic source may comprise the earth’s magnetic field, magnetic fields from electronics devices and/or magnetic fields from ferromagnets. It may be appreciated that due to the essentially ever present earth’s magnetic field, the magnetic field of the second magnetic source in accordance with the present invention preferably at least comprises the earth’s magnetic field.

The magnetic background noise is generally not constant. For example, based on the orientation and/or position of the magnetometer, the magnetic background noise may have a larger or smaller contribution to the net magnetic field that is sensed by the magnetometer. The precise contribution of the magnetic background noise to the signal as detected by the magnetometer is therefore unknown, which reduces the accuracy with which the first magnetic field can be measured. The present inventors realized that the background noise can be filtered by providing a second magnetometer that senses the magnetic fields of the first and second magnetic sources and that is located further away from the first magnetic source than the first magnetometer. By having the second magnetometer further away from the first magnetic source, the second magnetometer senses relatively less magnetic field provided by the first magnetic source and relatively more magnetic field provided by the second magnetic source than the first magnetometer. The second magnetic field data may therefore be used to at least partially filter out the magnetic field provided by the second magnetic source as sensed by the first magnetometer.

To further improve the accuracy of the first and/or second magnetometer, the micropipette, replacement part or add-on device preferably comprises a thermometer. The sensing of magnetic fields can depend on the temperature of the magnetometer. For example, a magnetometer at a higher temperature senses a lower magnetic field strength of a magnetic source than a magnetometer at a lower temperature. To enable a correction for data fluctuations originating by varying temperatures, the micropipette, replacement part or add-on device preferably comprises a thermometer.

As mentioned above, the method according to the present invention, comprises storing magnetic field data as sensed by the first magnetometer in a first magnetometer data set and storing magnetic field data as sensed by the second magnetometer in a second magnetometer data set. In order to filter the magnetic field provided by the second magnetic source, processing the first and second magnetometer data sets may comprise comparing the first and second magnetometer data sets to filter the magnetic field provided by the second magnetic source as sensed by the first magnetometer with the magnetic field provided by the second magnetic source as sensed by the second magnetometer. Essentially, as the first and second magnetometers sense the second magnetic field in essentially the same strength, but the first magnetic field in a different strength due to their individually different distances to the first magnetic source, the actual contribution of the first magnetic source to the sensed magnetic field by the first magnetometer can be derived. As such, the position of the plunger can accordingly be more accurately be determined. Additionally, the direction vectors of the magnetic fields sensed by the magnetometers may be considered. This is particularly interesting when the second magnetic field is not homogeneous between the first and the second magnetometer. By considering the direction vectors of the second magnetic field sensed at the first magnetometer and at the second magnetometer, a potential inhomogeneity may be corrected for.

In order to allow for optimal filtering of the magnetic field provided by the second magnetic source, it is preferred that the first magnetometer and second magnetometer are located at a sufficient distance from each other. This distance may be the entire length of the micropipette, replacement part or of the add-on device, but it may also be less. For instance, the first magnetometer may be located on the top of the body, while the second magnetometer is located in the vicinity of the tip cone. For practical reasons, the distance between the first and second magnetometer may be between 0-10 cm. As the magnetometers are often connected to a single circuit board, the distance may also be between 0-5 cm or 0-25 mm, such as 0-10 mm.

The magnetometers may be located along a common physical axis (i.e. an axis on the micropipette or the add-on device). However, due to i.a. production errors the magnetometers may be slightly off the common physical axis. Alternatively, the magnetometers may be placed off axis on purpose. Having the magnetometers not aligned on a physical common axis may be favorable in case the second magnetic field is not homogeneous. The magnetometers are however preferably aligned along a common virtual axis (i.e. a programmed axis system)

By having the magnetometers located on at least a common virtual axis, the magnetometer data sets may be more easily and accurately be processed, e.g. compared. It is therefore preferred that the method further comprises calibrating the first and second magnetometers along a common virtual axis. Several calibration methods may be feasible. These include, but are not limited to, using inertial measurement units (IMU) that each comprise an accelerometer, or by using a faraday cage wherein a homogeneous magnetic field is applied. Alternatively, one may assume that the earth’s magnetic field is homogeneous within the distance between the magnetometers and compare the earth magnetic field vectors of the first magnetometer with the second magnetometer.

During use of the micropipette, the plunger button is pressed and/or released and the distances between the first magnetic source and the first magnetometer decreases and/or increase, respectively. This is detectable by the first magnetometer in time due to the change in magnetic field as sensed by the magnetometer. The first and second magnetometer data sets are processed to extrapolate the position of the plunger relative to the first magnetometer. By extrapolating the position of the plunger over time, or at certain time intervals, the movement of the plunger can be determined. This movement may be correlated to the volume of liquid obtained or released from the micropipette. Thus, by being able to accurately determine the position of the plunger it is possible to obtain accurate data on the volumes of liquid that has been pipetted.

In order to extrapolate this position, the first and second magnetometer data sets and optionally any further data sets (vide infra) are processed. The micropipette, replacement part or the kit of parts therefore may comprise a processing unit. Alternatively, the processing unit may be a remote processing unit. In case the processing unit is a remote processing unit, it may be required to send the first and second magnetometer data sets and optionally any of the other data sets to the processing unit. This may be achieved by a communication unit. Accordingly, the micropipette, replacement part or the kit of parts may comprise a communication unit. Typically, this communication unit comprises a chip that facilitates wireless communication standards or wired communication standards. Wireless communication for instance include Bluetooth, Bluetooth Low Energy Wi-Fi or wireless serial communication. Wired communication includes ethernet, universal serial bus (USB), inter-integrated circuit (I ² C) and IEEE 1394 (i.e. FireWire). It may also be appreciated that the communication unit can be used to communicate the processed data to e.g. a computer, to document the position of the plunger. This allows for easy retrieval and logging of the activity of the plunger, that may be advantageous for i.a. quality auditing.

Other components that may be used to further increase the accuracy of the position determined by extrapolating the data sets, are data relating to the acceleration and/or to the angular velocity of the movement of the micropipette. Accordingly, the micropipette, replacement part or addon device may further comprise an accelerometer and/or a gyroscope.

The sensors, i.a. the magnetometers, accelerometer and gyroscope, are typically connected to a single circuit board. An example of an electronic layout for a suitable circuit board is provided in Figure 5. Herein a power receiver (13) is connected to a power management circuit (14). The power receiver (13) may be a wireless charging coil or comprise charging contact points. The power management circuit may be connected to a battery (15). It may be appreciated that the power management circuit may also be connected to other components such as one or more sensors depending on the voltage operating range of the other components. Further, the power management circuit may be connected to a processor (17), which is typically connected to a communication unit (16). The processor is further illustrated to be connected to the first magnetometer (10) and the second magnetometer (11). The magnetometers may be connected through circuit communication standards (e.g. I ² C). The processor may further be connected to other sensors. These sensors can include a gyroscope (18), an accelerometer (19) and a thermometer (20). It may however be appreciated that further sensors can also be present. Further, connected herein describes that the components are linked in such a way that a signal may be transferred from one component to the next component.

The accelerometer may be used to sense the acceleration of movement of the micropipette to generate accelerometer data. This accelerometer data can also be stored in another data set (e.g. an accelerometer data set).

The gyroscope may be used to sense the angular velocity of movement and/or position of the micropipette to generate gyroscope data. This gyroscope data can also be stored in yet another data set (e.g. a gyroscope data set).

The accelerometer data and/or the gyroscope data sets may be processed accordingly, to increase the accuracy of the extrapolated position of the plunger. For instance, the gyroscope data set may optionally be processed to extrapolate the movement and/or position of the micropipette. The accelerometer data set may additionally or alternatively be processed to extrapolate the movement of the micropipette

It may be appreciated that the data sets may be stored on any suitable memory, for instance a local memory or a remote memory.

For the purpose of clarity and a concise description features are described herein as part of the same or separate embodiments, however, it will be appreciated that the scope of the invention may include embodiments having combinations of all or some of the features described.