Bioprinter and method for calibrating a bioprinter

Abstract

A bioprinter (1) comprises at least one print head (4a, 4b, 4c) having a nozzle (5), a print bed (20) on which the print head (4a, 4b, 4c) is arranged to print ink, an ultrasonic sensor arrangement arranged at the print bed (20), a controller (7) arranged to control movement of the print head / nozzle (4a, 4b, 4c; 5) based on information from the ultrasonic sensor arrangement and to perform calibration of the print head / nozzle (4a, 4b, 4c; 5).

Description

TECHNICAL FIELD

[0001] The present disclosure relates to the field of additive manufacturing of biological materials. In particular, the present disclosure relates to a bioprinter and a method for calibrating print heads / nozzles in a bioprinter. BACKGROUND

[0002] Printing as an additive manufacturing technique is gaining its due importance for its ability to spatially control the placement of cells, biological materials and biomolecules. As a result, it offers unlimited possibilities for the future of tissue and organ regeneration, basic research and drug screening. A 3D printer is capable of dispensing material while moving along the X, Y and Z directions, which enables the design of complex structures from bottom to top. Furthermore, since this technique can be combined with CAD / CAM techniques using medical images of patients, it allows for the biofabrication of 3D structures with a biomimetic shape unique to the target tissue or organ.

[0003] One important aspect of a multi-head bioprinter is its ability to precisely print all of its print heads at the same location. During assembly and use, the orientation of the print heads can deviate slightly, causing the position of the end effector, i.e. the nozzle tip, to deviate from its ideal position.

[0004] To achieve high quality printing using multiple heads, a precise method for calibrating the end effector is needed. For example, in the case of the BIO X TM Instrument, the end effector must be calibrated with a precision of 20-50um.

[0005] Current methods for automatic calibration include touching a plastic joystick with the printer nozzle. This method is suboptimal for several reasons: the end effector sometimes misses the joystick; the joystick is prone to breaking; all nozzles touch the same joystick, which can cause cross-contamination. Therefore, a robust method for contactless calibration is needed. SUMMARY

[0006] It is an object of the present invention to provide an improved or at least alternative bioprinter, and a method for calibrating print heads / nozzles in the bioprinter.

[0007] According to a first aspect, there is provided a bioprinter comprising: at least one print head provided with a nozzle; a print bed on which the print head is arranged to print ink; an ultrasonic sensor arrangement arranged at the print bed, the ultrasonic sensor arrangement comprising: a first sensor arrangement arranged to provide a first ultrasonic cone extending in a first direction perpendicular to an extension of the nozzle; and a second sensor arrangement arranged to provide a second ultrasonic cone extending in a second direction perpendicular to the extension of the nozzle, wherein the first and second sensor arrangements are arranged to detect when the nozzle enters its ultrasonic cone, preferably the first and second directions are perpendicular to each other. A controller is arranged to control movement of the print head / nozzle and to perform a calibration of the print head / nozzle, the calibration comprising controlling the print head / nozzle according to a calibration scheme and determining a relationship between the nozzle and the first and second ultrasonic cones based on detections made by the first and second sensor arrangements when the nozzle is moved according to the calibration scheme, whereby a calibrated position of the print head / nozzle can be obtained in at least the first and second directions and preferably in a direction along the extension of the nozzle, and the controller is further arranged to control movement of the print head / nozzle according to the performed calibration.

[0008] The bioprinter can be a bioprinter for dispensing ink.

[0009] The first and / or second sensor arrangement can comprise an ultrasonic sensor and at least one solid surface arranged to direct a beam from the sensor thereby forming a cone extending in the first / second direction perpendicular to the extension of the nozzle.

[0010] Alternatively, the first and / or second sensor arrangement can comprise an ultrasonic sensor and a curved sound conduit arranged to direct a beam from the sensor thereby forming a cone extending in the first / second direction perpendicular to the extension of the nozzle.

[0011] According to a second aspect, there is provided a method for calibrating a print head in a bioprinter, the print head being provided with a nozzle, the bioprinter further comprising: a print bed, the print bed being arranged with the print head to print ink thereon; and an ultrasonic sensor arrangement arranged at the print bed, the ultrasonic sensor arrangement comprising: a first sensor arrangement arranged to provide a first ultrasonic cone extending in a first direction perpendicular to an extension of the nozzle; and a second sensor arrangement arranged to provide a second ultrasonic cone extending in a second direction perpendicular to the extension of the nozzle, wherein the first sensor arrangement and the second sensor arrangement detect when the nozzle enters the ultrasonic cones, preferably the first direction and the second direction are perpendicular to each other. The method comprises the steps of: controlling the print head / nozzle according to a calibration scheme, and determining a relationship between the nozzle and the first ultrasonic cone and the second ultrasonic cone based on the detections by the first sensor arrangement and the second sensor arrangement when the print head / nozzle is moved according to the calibration scheme, whereby a calibrated position of the print head / nozzle can be obtained in at least the first direction and the second direction, and preferably in a direction along the extension of the nozzle.

[0012] controlling the nozzle according to the calibration scheme, and determining a relationship between the nozzle and the first ultrasonic cone and the second ultrasonic cone based on the detections by the first sensor arrangement and the second sensor arrangement when the nozzle is moved according to the calibration scheme, can comprise:

[0013] - controlling the nozzle to move according to a position determination scheme for controlling the position of the nozzle in the second direction relative to the first ultrasonic cone to detect the position of the boundary of the first ultrasonic cone in the second direction by means of the first ultrasonic sensor arrangement,

[0014] - controlling the nozzle to move according to a position determination scheme for controlling the position of the nozzle in the first direction relative to the second ultrasonic cone, the position determination scheme being based on the position of the boundary of the first ultrasonic cone and a spatial relationship between the first ultrasonic sensor arrangement and the second ultrasonic sensor arrangement to detect the position of the boundary of the second cone in the first direction by means of the second ultrasonic sensor arrangement,

[0015] - whereby the position of the nozzle in the first direction and the second direction can be determined based on the positions of the boundaries of the first ultrasonic cone and the second ultrasonic cone.

[0016] controlling the nozzle according to the calibration scheme, and determining a relationship between the nozzle and the first ultrasonic cone and the second ultrasonic cone based on the detections by the first sensor arrangement and the second sensor arrangement when the nozzle is moved according to the calibration scheme, can further comprise:

[0017] - controlling the nozzle movement according to a nozzle position determination scheme controlling the nozzle in the second direction relative to the first ultrasonic cone, the position determination scheme being based on at least the position of the border of the second ultrasonic cone and the spatial relationship between the first ultrasonic sensor device and the second ultrasonic sensor device, to detect an updated position of the border of the first ultrasonic cone in the second direction by means of the first ultrasonic sensor device, whereby the position of the nozzle in the first and second direction is determined based on the updated positions of the border of the first ultrasonic cone and the border of the second ultrasonic cone.

[0018] The method can further comprise the step of determining the position of the nozzle in a direction extending substantially along the extension of the nozzle based on the knowledge of the position of the nozzle in the first and second direction.

[0019] The method can further comprise controlling the nozzle to a start position outside the first and second ultrasonic cones in a direction along the extension of the nozzle, and

[0020] - controlling the nozzle from the start position according to an ultrasonic cone finding mode to detect the first ultrasonic cone, whereupon the control according to the calibration scheme is started.

[0021] With the above described bioprinter and method for calibration, the print head, the plurality of print heads, the multi head or the replaceable print head in the bioprinter can be calibrated such that printing with different print heads at the same location at the print bed becomes possible. Thus, deviations of the orientation of the print head and the nozzles arranged thereon, which can occur during assembly and use, and which cause the position of the nozzles and nozzle tips to deviate from their ideal position, can be minimized. The present bioprinter and method provide a robust bioprinter for contactless, automatic calibration. BRIEF DESCRIPTION OF DRAWINGS

[0022] Figure 1 A side view of the bioprinter / bioprinter is shown.

[0023] Figure 2 A print bed of the bioprinter is shown from a top view (left) and a side view (right). Figure 1

[0024] Figure 3 A method for calibrating a print head / nozzle in a bioprinter is shown schematically. DETAILED DESCRIPTION

[0025] Printing as an additive manufacturing technique is gaining the attention it deserves for its ability to spatially control the placement of cells, biomaterials and biomolecules. It thus offers unlimited possibilities for the future of tissue and organ regeneration, basic research and drug screening.

[0026] ​A 3D bioprinter / bioprinter is capable of dispensing material while moving in the X, Y and Z direction. This enables to design complex constructs from bottom to top. Furthermore, since the technology can be combined with CAD / CAM technology using medical images of a patient, the technology allows to biofabricate a 3D structure of a biomimetic shape unique to a target tissue or organ.

[0027] Figure 1 a An example of a bioprinter / bioprinter 1 according to the present disclosure is disclosed. The bioprinter 1 can be used to manufacture a three-dimensional designed biological tissue. The bioprinter can be used to print a construct suitable for use in an application selected from the group consisting of implantation in an animal or human body, for example to repair or replace tissue, topical application, cosmetic application, drug testing, drug discovery application or as a disease model, or for other research, investigation or development purposes in the pharmaceutical, medical, chemical, personal care, skin care or cosmetic industry, or any other industry in which a construct can be used using 3D printing.

[0028] The bioprinter 1 comprises a print bed 20. The print bed 20 comprises for example a petri dish. A petri dish is defined as a shallow cylindrical glass or plastic lid dish used for culturing cells. In one example, the print bed 20 comprises a microwell, also known as a microplate. In one example, the print bed 20 comprises a glass slide.

[0029] The bioprinter further comprises at least one print head 4a, 4b, 4c. The bioprinter 1 can comprise one print head, multiple heads or a plurality of print heads. In Figure 1 In one example, the bioprinter is shown with three print heads 4a, 4b, 4c. The print heads can be replaceable. The print heads can be arranged to print ink, bioink, in turn on the print bed 20. Examples of print heads comprise a pneumatic extrusion head, a syringe pump head, an inkjet head, a high temperature extrusion head, etc.

[0030] The at least one print head 3 is provided with a nozzle 5, which can be detachably arranged on the print head. The nozzle can be an extrusion needle. The print head 3 and the print bed 20 can be moved relative to each other. Thereby, the bioprinter is arranged to print a 3D article on the print bed by controlling the extrusion through the nozzle 5 by means of an extrusion element and by controlling the relative movement between the print bed and the nozzle / print head.

[0031] In one example, the movement of the nozzle / print head is controlled according to a predetermined scheme while the position of the print bed is fixed. In one example, the movement of the print bed is controlled according to a predetermined scheme while the position of the nozzle / print head is fixed.

[0032] As Figure 1 and Figure 2As shown, an ultrasonic sensor device is arranged at the print bed 20. The ultrasonic sensor device includes: a first sensor device 6a, arranged to provide a first direction perpendicular to the extension of the nozzle 5. Figure 2 A first ultrasonic cone extending in the x-direction of the nozzle 5; and a second sensor device 6b, arranged to provide in a second direction perpendicular to the extension of the nozzle 5. Figure 2 A second ultrasonic cone extends in the y-direction (as shown in the image). A first sensor device 6a and a second sensor device 6b are arranged to detect when the nozzle 5 enters its ultrasonic cone. Preferably, the first and second directions are perpendicular to each other, such as... Figure 2 As shown.

[0033] An ultrasonic sensor device can be used to calibrate the position of at least one printhead / nozzle.

[0034] Both the first sensor device 6a and the second sensor device 6b may include an ultrasonic sensor and an ultrasonic distance sensor. The ultrasonic distance sensor measures distance by emitting sound and measuring the time of flight of the sound reflected back to the sensor from an object in front of it. In the case of multiple reflections at different distances, the sensor only detects the most recent reflected sound. The emitted sound can be considered as a cone. The ultrasonic distance sensor can detect small objects made of both plastics (such as polypropylene) and metals (such as stainless steel), which is why nozzles made of different materials can be used. For example, a sensor such as the SICK UC4-13347 can be used. Such sensors have a measurement resolution of 100 μm or higher and repeatability of ±0.15%.

[0035] The ultrasonic sensor can be vertically positioned at the printing bed so that the emitted sound cone is oriented in the x / y direction.

[0036] The ultrasonic sensor used can measure distances up to 150 mm from an object with a resolution of 200 μm.

[0037] The ultrasonic sensor can be placed anywhere on the print bed 20, as long as it is formed in an ultrasonic cone extending in a first / second direction perpendicular to the extension of the nozzle.

[0038] The first sensor device 6a and / or the second sensor device 6b may include an ultrasonic sensor and at least one solid surface (not shown), said at least one solid surface being arranged to guide a beam from the sensor, thereby forming a cone extending in a first / second direction perpendicular to the extension of the nozzle.

[0039] For example, the surface can be arranged at a 45 degree angle to the beam from the ultrasonic sensor. In this embodiment, the ultrasonic sensor of the sensor device can be oriented horizontally in the bioprinter 1 to better utilize the available space at the print bed 20. Horizontally mounting the ultrasonic sensor requires re-directing the sound beam so that the sound cone can be emitted in the x-direction / y-direction.

[0040] Alternatively, the first sensor device and / or the second sensor device can comprise an ultrasonic sensor and a curved sound conduit (not shown) arranged to direct the beam from the sensor so as to form a cone extending in a first direction / second direction perpendicular to the extension of the nozzle.

[0041] The bioprinter further comprises a controller 7 arranged to control the movement of the print head 4a, 4b, 4c / nozzle 5. The controller 7 is arranged to perform a calibration of the print head 4a, 4b, 4c / nozzle 5 as Figure 3 indicated. The calibration comprises controlling 100 the print head / nozzle according to a calibration scheme, and determining 200 the relationship between the nozzle 5 and the first and second ultrasonic cones based on detection by the first and second sensor devices 6a, 6b as the nozzle 5 is moved according to the calibration scheme, from which a calibrated position of the print head / nozzle can be obtained 300 in at least the first and second directions, and preferably in a direction along the extension of the nozzle 5.

[0042] The controller 7 can further be arranged to control the movement of the print head / nozzle according to the performed calibration.

[0043] Controlling the nozzle according to a calibration scheme, and determining the relationship between the nozzle and the first and second ultrasonic cones based on detection by the first and second sensor devices as the nozzle is moved according to the calibration scheme can comprise:

[0044] - controlling the nozzle movement according to a position determination scheme for controlling the position of the nozzle in the second direction relative to the first ultrasonic cone, to detect the position of the boundary of the first ultrasonic cone in the second direction by means of the first ultrasonic sensor device,

[0045] - controlling the nozzle movement according to a position determination scheme for controlling the position of the nozzle in the first direction relative to the second ultrasonic cone, based on the position of the boundary of the first ultrasonic cone and the spatial relationship between the first and second ultrasonic sensor devices, to detect the position of the boundary of the second cone in the first direction by means of the second ultrasonic sensor device,

[0046] - from which the position of the nozzle in the first and second directions can be determined based on the position of the boundaries of the first and second ultrasonic cones.

[0047] controlling the nozzle according to the calibration scheme and determining the relationship between the nozzle and the first and second ultrasonic cones based on the detections by the first and second sensor devices as the nozzle is moved according to the calibration scheme can further comprise:

[0048] - controlling the nozzle movement according to a position determination scheme for controlling the position of the nozzle in the second direction relative to the first ultrasonic cone, the position determination scheme being based on at least the position of the boundary of the second ultrasonic cone and the spatial relationship between the first and second ultrasonic sensor devices, whereby the updated position of the boundary of the first ultrasonic cone in the second direction is detected by means of the first ultrasonic sensor device, from which the position of the nozzle in the first and second directions is determined based on the updated positions of the boundaries of the first and second ultrasonic cones.

[0049] The method can further comprise the step of determining the position of the nozzle in a direction extending substantially along the extension of the nozzle based on the knowledge of the position of the nozzle in the first and second directions.

[0050] The method can further comprise controlling the nozzle to a start position outside the first and second ultrasonic cones in a direction along the extension of the nozzle, and

[0051] - controlling the nozzle from the start position according to an ultrasonic cone finding mode for detecting the first ultrasonic cone, after which the control according to the calibration scheme is started.

Claims

1. A bioprinter (1) comprising: at least one print head (4a, 4b, 4c) provided with a nozzle (5); a print bed (20) on which the print head (4a, 4b, 4c) is arranged to print ink; an ultrasonic sensor arrangement arranged at the print bed (20), the ultrasonic sensor arrangement comprising a first sensor arrangement (6a) arranged to provide a first ultrasonic cone extending in a first direction perpendicular to an extension of the nozzle (5) and a second sensor arrangement (6b) arranged to provide a second ultrasonic cone extending in a second direction perpendicular to the extension of the nozzle (5), wherein the first sensor arrangement (6a) and the second sensor arrangement (6b) are arranged to detect when the nozzle (5) enters its ultrasonic cone; and a controller (7) arranged to control movement of the print head / nozzle, the controller (7) being arranged to perform a calibration of the print head / nozzle, the calibration comprising controlling the print head / nozzle according to a calibration scheme and determining a relation between the print head / nozzle and the first and second ultrasonic cones based on detections made by the first and second sensor arrangements (6a, 6b) when the nozzle (5) is moved according to the calibration scheme; wherein in the calibration the controller (7) is arranged to control the nozzle to move according to a position determination scheme for the nozzle in the second direction relative to the first ultrasonic cone, wherein the first sensor arrangement (6a) is arranged to detect a position of a boundary of the first ultrasonic cone in the second direction, wherein the controller is arranged to control the nozzle to move according to a position determination scheme for the nozzle in the first direction relative to the second ultrasonic cone, the position determination scheme being based on the position of the boundary of the first ultrasonic cone and a spatial relation between the first and second sensor arrangements (6a, 6b), wherein the second sensor arrangement is arranged to detect a position of a boundary of the second cone in the first direction, whereby a position of the nozzle in the first and second directions can be determined based on the positions of the boundaries of the first and second ultrasonic cones, whereby a calibrated position of the print head / nozzle in at least the first and second directions can be obtained, and the controller (7) is further arranged to control movement of the print head / nozzle according to the performed calibration.

2. The bioprinter (1) according to claim 1, wherein the first and / or second sensor arrangement (6a, 6b) comprises an ultrasonic sensor and at least one solid surface arranged to guide a beam from the sensor, thereby forming a cone extending in the first / second direction perpendicular to an extension of the nozzle (5).

3. The bioprinter (1) according to claim 1 or 2, wherein The first sensor arrangement (6a) and / or the second sensor arrangement (6b) comprises an ultrasonic sensor and a curved sound conduit arranged to guide a beam from the sensor forming a cone extending in the first direction / second direction perpendicular to the extension of the nozzle (5).

4. The bioprinter (1) according to claim 1, wherein The first direction and the second direction are perpendicular to each other.

5. The bioprinter (1) according to claim 1, wherein A calibrated position of the print head / nozzle in a direction along the extension of the nozzle (5) can be obtained.

6. A method for calibrating a print head (4a, 4b, 4c) in a bioprinter (1), the print head being provided with nozzles (5), the bioprinter (1) further comprising: a print bed (20) on which the print head (4a, 4b, 4c) is arranged to print ink; and an ultrasonic sensor arrangement arranged at the print bed (20), the ultrasonic sensor arrangement comprising a first sensor arrangement (6a) arranged to provide a first ultrasonic cone extending in a first direction perpendicular to the extension of the nozzle (5) and a second sensor arrangement (6b) arranged to provide a second ultrasonic cone extending in a second direction perpendicular to the extension of the nozzle (5), wherein the first and second sensor arrangements detect when the nozzle enters an ultrasonic cone, the method comprising the steps of: controlling (100) the print head / nozzle according to a calibration scheme, and determining (200) the relationship between the nozzle (5) and the first and second ultrasonic cones based on the detection by the first and second sensor arrangements (6a, 6b) when the print head / nozzle is moved according to the calibration scheme, wherein the nozzle is controlled to move according to a position determination scheme controlling the nozzle in the second direction relative to the first ultrasonic cone to detect the position of the border of the first ultrasonic cone in the second direction by means of the first sensor arrangement and according to a position determination scheme controlling the nozzle in the first direction relative to the second ultrasonic cone based on the position of the border of the first ultrasonic cone and the spatial relationship between the first and second sensor arrangements to detect the position of the border of the second cone in the first direction by means of the second sensor arrangement, whereby the position of the nozzle in the first and second directions can be determined based on the positions of the borders of the first and second ultrasonic cones, whereby a calibrated position of the print head / nozzle in at least the first and second directions can be obtained (300).

7. The method of claim 6, further comprising the step of: determining the position of the nozzle in a direction extending substantially along the extension of the nozzle based on the knowledge of the position of the nozzle in the first and second directions.

8. The method according to any of claims 6-7, further comprising: controlling the nozzle to a start position outside the first and second ultrasonic cones in a direction along the extension of the nozzle, and controlling the nozzle to a start position outside the first and second ultrasonic cones in a direction along the extension of the nozzle, and controlling the nozzle to move from the start position to detect the first ultrasonic cone, whereupon control according to the calibration scheme is initiated.

9. The method of claim 6, wherein, The first direction and the second direction are perpendicular to each other.

10. The method of claim 6, wherein, A calibration position of the printhead / nozzle in a direction along the extension of the nozzle (5) can be obtained.

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