FIELD OF THE INVENTION

The invention relates to a method for 3D-printing a device and 3D-printer for 3D-printing a device. The invention further relates to the device as such. The invention also relates to a method for operating a (microfluidic) device.

BACKGROUND OF THE INVENTION

3D-printing of microfluidic AFM cantilevers is known in the art. For instance, Robert C.L.N. Kramer et al. in Lab Chip, 2020, 20, 311, DOI: 10.1039/c91c00668k, describes that microfluidic atomic force microscopy (AFM) cantilever probes have all the functionalities of a standard AFM cantilever along with fluid pipetting. They have a channel inside the cantilever and an aperture at the tip. Such probes are useful for precise fluid manipulation at a desired location, for example near or inside cells. They are typically made by complex microfabrication process steps, resulting in expensive probes. Robert C.L.N. Kramer et al. used two different 3D additive manufacturing techniques, stereolithography and two-photon polymerization, to directly print ready -to-use microfluidic AFM cantilever probes. According to Robert C.L.N. Kramer et al., this approach has considerably reduced the fabrication time and increased the design freedom. One of the probes, 564 pm long, 30 pm wide, 30 pm high, with a 25 pm diameter channel and 2.5 pm wall thickness had a spring constant of 3.7 N m ^-1 and the polymer fabrication material had an elastic modulus of 4.2 GPa.

Bayindir et al, “Polymer microcantilevers fabricated via multiphoton absorption polymerization”, applied physics letters 86, pages 641050-1 to 641050-3, 2005, describes the use of multiphoton absorption polymerization to fabricate a series of microscale polymer cantilevers.

SUMMARY OF THE INVENTION

As indicated by Robert C.L.N. Kramer et al., which is herein incorporated by reference, and also referring to references cited therein, “TVo two cells are identical. Moreover, cells are constantly responding to internal and external signals which result in highly dynamic cellular characteristics, for example in cell type and cellular state. This means that even purified cell populations are often composed of a heterogeneous mix of cells and bulk analyses often result in an averaged representation of a cell population's cellular characteristics. Fully unravelling cellular complexity in both healthy and diseased states will therefore require characterization and manipulation at single-cell resolution. Microsystem technologies are suitable for this task due to their similar size scale to the cells under study. To sort cells, passive methods such as micropillar arrays4 or active methods like microfluidic acoustic resonance have been used. To accurately quantify single cell characteristics, micro/nano-mechanical resonators have been used to determine cell density, growth rate and response to drugs. To manipulate single cells, atomic force microscopy (AFM) based methods are suitable. This manipulation of single cells can provide information on cellular characteristics such as elastic modulus, adhesion strength, and response to mechanical stimuli. With the advent of the FluidFM technique, simultaneous precise force control and (sub)picolitre volume fluid manipulation inside a cell has become possible. The technique uses an AFM cantilever with an internal channel and aperture at the tip. These hollow microcantilever probes are fabricated by standard clean room microfabrication techniques with nanometer precise control over their shape and size. However, despite considerable progress in microfabrication, microfluidic AFM cantilever probes are not widely available due to the complex process steps leading to a high cost per probe. It takes at least two weeks of fabrication with about 6 masks depending on the process. They also need a fluidic interface to be attached before they are ready for use. Furthermore, exploring novel functional prototypes with existing process steps is an even more expensive endeavor. 3D additive manufacturing technologies have recently emerged as new bottom-up microfabrication methods for biological applications. They offer easy, rapid, and cost-effective prototyping and production. They also expand the design freedom (complex designs) and design space (in 3D) to directly print novel devices. Among many capable 3D- printing techniques, stereolithography (ST) and two-photon polymerization (2PP) are able to print with micro- and sub-micrometer resolution, respectively. In both techniques, light illuminates a liquid (positive)negative photoresist, thereby locally (de)polymerizing it to form a solid structure. Commercial SL-systems are able to fabricate objects that can be several cubic centimeters in size with an accuracy of 20 pm and single- and two-photon polymerization setups have reached feature sizes of 430 nm and 9 nm, respectively. These 2PP nanometer feature sizes come at the cost of printing speed, hence combination with SL-printing is desirable from a time reduction point of view. Using 2PP, the following structures have been printed by others: embedded microfluidic channels with internal pillars to trap biological entities, a doubly- clamped suspended microchannel resonator, and custom designed AFM tips on commercial tip-less cantilevers. Furthermore, 2PP printing has been combined with ST printing to print a micro-filter. However, to the best of our knowledge, a complete polymeric microfluidic AFM cantilever as a ready-to-use device has not been printed so far." Robert C.L.N. Kramer et al., further indicates that “ several types of microfluidic AFM cantilevers were directly printed onto an SL-printed fluidic interface. Their functionality was proved by using them to image surface topography, dispense fluid, puncture cells, and aspirate selected cell(s)” .

There appears to be a desire to (further) improve production of cantilevers and/or to provide (microfluidic) cantilevers which allow a higher resolution and/or which are better controllable or with which processes can be executed in a better controlled way. Process in the art may imply large design-test cycles. Further, 3D printing suspended elements appear to suffer from reproduction issues.

Hence, it is an aspect of the invention to provide an alternative method for 3D- printing a device comprising a cantilever, which preferably further at least partly obviates one or more of above-described drawbacks. The present invention may have as object to overcome or ameliorate at least one of the disadvantages of the prior art, or to provide a useful alternative.

In a first aspect, the invention provides a method for 3D-printing a device comprising a cantilever. Especially, the method comprises a preparation stage, resin providing stage, and a 3D printing stage. In embodiments, the preparation stage may comprise providing (i) a main body, and (ii) a support structure. In embodiments, the main body may comprise a cantilever support and an (planar) interface element. Especially, the interface element may comprise a first face and a second face. Especially, the first face and the second face are different faces, and may have a mutual angle of e.g. about 60 - 120°. In embodiments, the cantilever support may be arranged on the first face. Further, especially the support structure may be configured at a first distance (dl) from the second face. In embodiments, the first distance (dl) may be selected fromm the range of 50 - 500 pm. In embodiments, the resin providing stage may comprise providing a droplet at least partially onto the first face and at least partially onto the support structure, wherein the droplet comprises a photosensitive (liquid) resin. Especially, the resin may be configured to cure when exposed to first radiation. Yet, in embodiments the 3D printing stage may comprise generating the cantilever by exposing the resin to first radiation. Especially, the cantilever may protrude from the cantilever support, especially beyond the second face. Therefore, in embodiments the invention provides a method for 3D-printing a device comprising a cantilever, wherein the method comprises: (A) a preparation stage comprising providing (i) a main body, and (ii) a support structure; wherein the main body comprises a cantilever support and an (planar) interface element, wherein the interface element comprises a first face and a second face (different from the first face), wherein the cantilever support is arranged on the first face; wherein the support structure is configured at a first distance (dl) from the second face, wherein the first distance (dl) is selected from the range of 50 - 500 pm; (B) a resin providing stage comprising providing a droplet at least partially onto the first face and at least partially onto the support structure, wherein the droplet comprises a photosensitive (liquid) resin configured to cure when exposed to first radiation; and (C) a 3D printing stage comprising generating the cantilever by exposing the resin to first radiation, wherein the cantilever protrudes from the cantilever support and beyond the second face.

With such a method, a suspending cantilever may be made, for instance for a microfluidic device or for other applications. For instance, the suspending cantilever may be used for AFM imaging applications or other applications where a microscale cantilever may be needed. With such a method, a 3D cantilever may be 3D printed with relatively high resolution. Robust structure may be made, in a relatively well controlled way. Further, the present invention allows relatively high precision for parts where high precision is beneficial, but also allows generation of other parts with lower resolution 3D printing where a high resolution is not necessary.

Cantilevers are known in the art. Amongst others, the invention provides a suspending cantilever, e.g. for AFM or microfluidic applications. Especially, the invention provides a microfluidic AFM cantilever. Hence, in embodiments the cantilever comprises a microfluidic AFM cantilever. However, the invention is not limited to microfluidic AFM cantilevers.

Here below, embodiments in relation to the method of the invention, but (effectively) also in relation to the device of the invention are described.

As indicated above, the method comprises a preparation stage, a resin providing stage, and a 3D printing stage.

Especially, during the preparation stage a main body is provided. The main body may comprise a cantilever support and an interface element. The cantilever support may especially be a part from which the cantilever is grown during the 3D printing stage. The cantilever support may in embodiments be functionally coupled to the interface element or may in other embodiments be comprised by the interface element.

The interface element may be used to functionally couple the cantilever to a device, like an AFM apparatus. The interface element may also be a microfluidic chip. In embodiments, the interface element may be used to mount on an atomic force microscopy (AFM) holder or may be used for connection between the 3D printed microfluidic AFM cantilever and another device.

The interface element may also be 3D printed, though this is not necessarily the case. The cantilever support may also be 3D printed, though this is not necessarily the case. The interface element and the cantilever may be of different materials. The cantilever support and the cantilever may be of different materials, but may also comprise essentially the same materials. Using essentially the same materials may facilitate a good connection between the cantilever support and the cantilever. Especially, the cantilever support may be arranged on the first face. In embodiments, the cantilever support may have a dome shape. However, other shapes may also be possible. In embodiments, the cantilever support may approximate a dome shape.

The term “approximate” and its conjugations herein, such as in “to approximate a shape”, may refer to being nearly identical to, especially identical to, the following term, for example nearly identical to a circular sector or a semi-cylindrical shape. For example, a welding section may define a circular sector but for a defect. Similarly, for example, the rounded shape defined by the welding section may not be perfectly round but slightly ellipsoidal. In particular, an object approximating a first shape may herein refer to: a first shape realization encompassing the object, wherein the first shape realization is defined as the smallest encompassing shape of the (2D or 3D, respectively) object wherein the first shape realization has the shape of the first shape, wherein a ratio of the area (volume) of the first shape realization to the area (volume) of the object may be < 1.2, especially < 1.1, such as <1.05, especially <1.02. For instance, a welding section may approximate a semi-cylindrical shape, wherein the first shape realization may be defined as the smallest encompassing semi-cylindrical shape of the welding section, wherein a ratio of the volume of the first shape realization to the volume of the welding section is < 1.2, especially, especially < 1.1, such as <1.05, especially <1.02, including 1. Further, if the dimensions of the first shape are defined, the term approximate may refer to the object and the first shape being superimposable (in 2D or 3D, respectively) such that an intersection between the object and the first shape covers at least n% of the object and at least n% of the shape, wherein n is at least 90%, such as at least 95%, especially at least 98%, such as at least 99%, including 100%.

Especially, the interface element comprises a first face and a second face. The latter face is a face different from the former face. Especially, the interface element may comprise a planar first face. Hence, in embodiments the interface element may be a planar interface element. The second face may also be planar. The first face and the second face may especially have a mutual angle different from 0 or 180°. In particular, in embodiments, the (mutual) angle may be larger than 0° and smaller than 180°. Hence, in embodiments, the angle may be smaller than °180, such as < 160°, especially < 135°, such as < 120°. Especially, the first face and the second face may have a mutual angle selected from the range of about 60-120°. Hence, in embodiments planes defined by the first face and the second face are arranged at an angle selected from the range of 60 - 120°. More especially, the mutual angle is about 90°.

In embodiments, the first face and the second face may be separated by a third face arranged between the first face and the second face. For instance, in embodiments, the third face may be arranged between the first face and the second face with an angle of (about) 45° to the first face and of (about) 45° to the second face such that the first face and the second face are arranged at a mutual angle of (about) 90°.

Generally, however, the first face and the second face may be arranged adjacent to one another, such as by sharing an edge. Hence, in embodiments the first face is arranged adjacent to the second face. In further embodiments, the first face and the second face may share an interface, such as an edge.

To generate the suspending cantilever, it is herein proposed to have the 3D printable material, such as a resin, suspending. However, the printing of a (sideways) suspended structure may be challenging as the 3D printable material may shift or even drop if poorly supported. Herein, it is proposed that the 3D printable material is supported in order that it can provide a suspending cantilever. Hence, in the preparation stage, a support structure is provided, relatively close to the interface element, but at some distance, such that the 3D printable material can be deposited on both the interface element and the support structure. Therefore, the support structure may be configured at a first distance (dl) from the second face. Good results may be obtained with distance of at least about 20 pm, but not larger than about 1000 pm. Smaller distance may not allow long enough cantilever, and larger distances may lead to leakage of the 3D printable material. In specific embodiments, the first distance (dl) is selected from the range of 50 - 500 pm, especially from the range of 200 - 400 pm.

Hence, in embodiments, the support structure may be configured to support the droplet, especially during at least part of the resin providing stage, or especially during (at least part of) the 3D printing stage.

Further, the 3D printable material is provided. The 3D printable material is especially a resin, of which part can be converted by irradiating with light. This converts the resin that is irradiated with light into solid material, whereas surrounding resin, which is not irradiated or irradiated with a too low power, stay essentially unconverted. Hence, the method may comprise a resin providing stage comprising providing a droplet at least partially onto the first face and at least partially onto the support structure. Especially, the droplet comprises a photosensitive (liquid) resin configured to cure when exposed to first radiation. Especially, curing may comprise polymerization. Curing may (also) comprise cross-linking.

Hence, the cantilever is (then) generated in the 3D printing stage. By locally exposing the resin to radiation, locally the resin is converted into cured material. Step by step, the cantilever is built up, by locally irradiating the resin. This may be continued until the cantilever protrudes from the support, even beyond the second face. Hence, the cantilever may be grown from the cantilever support, especially over at least part of the gap between the interface element and the support structure. Non-cured resin may be washed away with a liquid, especially a solvent for the resin, or components of the resin. Hence, the 3D printing stage may comprise generating the cantilever by exposing the resin to first radiation, wherein the cantilever protrudes from the cantilever support and in specific embodiments beyond the second face.

The main body may be provided as such, i.e., comprising the interface element and the cantilever support. However, in other embodiments the latter may be provided on the former, especially in embodiments via 3D printing. Hence, in embodiments (of the method), the preparation stage may comprise (i) an interface providing substage comprising providing the interface element, and (ii) a cantilever support providing substage comprising arranging the cantilever support on the first face of the interface element.

In embodiments, the cantilever support providing substage may comprise one or more of stereolithography (SLA) or digital light processing (DLP). Both techniques are known in the art, and may rely on the use of light, typically in the UV-blue region of the spectrum (380 - 405 nm), to cure a photosensitive (viscous) resin. This resin, typically composed of epoxy or acrylic and methacrylic monomers, will polymerize and harden when exposed to specific wavelengths of light. As such light may shine locally on the resin to create specific shapes or patterns that compose each layer, a solid object can be formed and extracted from the otherwise liquid resin.

In embodiments, the cantilever support has a dome-like shape. In embodiments, the cantilever support comprises a facetted dome-like shape. In specific embodiments, the facets may have a hexagonal shape. For instance, in embodiments the faces may have dimensions selected from the range of 20-250 pm, such as 50-200 pm, like in embodiments 140 pm. Here, the dimensions may refer to a length and a width of the smallest enclosing rectangle. In specific embodiments, the cantilever support providing substage may comprise providing a plurality of hexagonal support sections to provide the cantilever support.

The overall size of the dome may be in the order of about 200-600 pm diameter, like about 250-550 pm in diameter, such as about 300-500 pm in diameter, and in the order of about 40-200 pm high, such as about 50-150 pm high, like about 75-125 pm high.

In specific embodiment, such as for microfluidic applications, the dome may be hollow. In embodiments, the inner diameter of a hollow dome may be selected from the range of about 100-550 pm in diameter, like selected from the range of 150-500 pm in diameter, such as selected from the range of about 200-350 pm in diameter. The outer diameter may be about at least 40 pm larger than the inner diameter.

When the cantilever support may be used for microfluidic applications, the cantilever support may have an opening directed to the interface element and an opening to (be) functionally coupled to the (hollow) cantilever.

Hence, in embodiments the cantilever support providing substage may comprise providing the cantilever support with a cantilever support opening, and wherein the 3D printing stage comprises generating the cantilever from the cantilever support opening.

To improve generation of the cantilever support on the first face, it appears useful to apply a reflective first face. This may allow a substantially exact generation of the cantilever support element on the first face. Hence, a reflective element, such as a reflective layer, may be comprised by the first face. For instance, a reflective layer may be configured on the first face (whereby effectively the first face may at least partly be defined by the reflective layer).

Therefore, in embodiments the interface providing substage comprises arranging a reflective element on the first face, and wherein the cantilever support providing substage comprises locating the reflective element and positioning the cantilever support based on the location of the reflective element. In embodiments, the reflective element, such as a reflective layer, may be provided by sputtering of the reflective layer material on the first face of the interface element.

Therefore, the phrase “is arranged on the first face” may refer to a direct arrangement on the first face, but it may also refer to an arrangement on an (optional) reflective element on the first face. As the reflective element may be partially disrupted (see also below), the phrase “is arranged on the first face” may refer to an at least partial arrangement on the first face and an at least partial arrangement on the reflective element on the first face. Reflective material may especially be metals. In specific embodiments, the reflective element may comprise a reflective layer material, especially a metal selected from the group comprising gold, silver, aluminum, and titanium. Combinations of two or more metals may also be applied. Especially, the reflective element may be relatively thin, like in the range of about 0.5-10 nm, such as about 1-5 nm. During the generation of the cantilever support on the interface element, the reflective layer may at least partly melt and thereby at least partly be disrupted. Therefore, in embodiments between the first face and the cantilever support, at least part of the reflective layer may be disrupted. Hence, in embodiments at the interface of the interface element and the cantilever support, reflective material may be present in the cantilever support (material). In specific embodiments, the reflective element comprises a reflective layer having a thickness (or height) selected from the range of 1-5 nm. Too thin layers may be unstable, whereas too thick layers may impede the 3D printing of the cantilever support.

The main body may be configured in a body holder, at least during the resin providing stage and the generation of the cantilever. As the cantilever support may be configured in a body holder (at least during the resin providing stage and the generation of the cantilever (i.e. the 3D printing stage)), also the support structure may be configured in the body holder. In embodiments, the main body may be supported by (relatively small) beams, which are used to arrange the main body in the right position. After generation of the cantilever, the main body may be removed from the body holder. For instance, the (relatively small) beams may be breakout beams. Therefore, in embodiments the preparation stage comprises providing the main body connected to a main body holder via breakout beams. In embodiments, the breakout may also be 3D printed. Hence, in specific embodiments the preparation stage may comprise providing a 3D printed main body connected to a main body holder via 3D printed breakout beams. For instance, the breakout beams may be printed via stereolithography (SLA) or digital light processing (DLP).

As indicated above, between the support structure and the interface element there may be a gap. The (produced) cantilever may bridge (at least part of) the gap. During 3D printing thereof, the cantilever may be 3D printed layer by layer in the direction of the support structure, until it may even be over the support structure in some embodiments. Therefore, in embodiments the second face and the support structure are separated by a gap providing the first distance (dl), wherein the cantilever bridges the gap. In specific embodiments, the cantilever may have a cantilever length L (along an axis of elongation of the cantilever). In embodiments, the axis of elongation may be parallel to the first face. Further, in embodiments the axis of elongation may be perpendicular to the second face. In embodiments, the cantilever length L may be at least 50 gm, such as at least about 100 gm, like especially at least about 150 pm. Yet even the cantilever length may be at least about 200 pm. In specific embodiments, the cantilever length L may be at least 250 pm. In embodiments, the cantilever length may be larger than the first distance. The length of the cantilever may be determined along an axis of elongation of the cantilever. The axis of elongation may especially connect geometric centers of cross-sections of the cantilever (like e.g. the (body) axis of a cylinder or the body axis of a beam, which may in such embodiments also be an axis of elongation as well as a symmetry axis).

As indicated above, the cantilever may be 3D printed layer by layer. Further, the cantilever may have an axis of elongation. In specific embodiments, the 3D printed layers may be arranged perpendicular to the axis of elongation. However, in further embodiments, the 3D printed layers may be arranged slanted relative to the axis of elongation. In specific embodiment the 3D printing stage may comprise sequentially generating cantilever sections of the cantilever from the cantilever support, wherein the cantilever sections are arranged at (respective) angles a _c to an axis of elongation of the cantilever, wherein the angles a _c are (independently) selected from the range of 30° - 60°. Yet further, in specific embodiments the cantilever sections may have (respective) length(s) L _s along the axis of elongation, wherein the length(s) L _s is (are) selected from the range of 0.05-15 pm, more especially 0.05-12 pm, such as about 0.1-10 pm, like more especially selected from the range of 0.5-10 pm, such as selected from the range of 2-6 pm. Hence, the layers may be relatively thin layers (with the thickness defined essentially parallel to the axis of elongation).

For the 3D printing stage of the cantilever, especially 2-photon polymerization may be used, which allows a relatively high precision. Two-photon polymerization as a direct laser writing technique allows for creating complex three-dimensional structures down to feature sizes on the order of about 100 nm, or even lower. Key elements of two-photon polymerization are lasers providing femtosecond pulses, suitable photosensitive materials (photoresists), a precise positioning stage and a computer to control the procedure. Two-photon polymerization is a non-linear optical process based on the simultaneous absorption of two photons in a photosensitive material (photoresist). This process changes the photosensitive material, i.e., it leads to a polymerization, especially by activating so-called photo-initiators in the resist. These may turn into radicals that polymerize the resist locally. In a subsequent step, the non-polymerized photoresist may be washed out to uncover the structure. Two-photon absorption may require relatively high intensities. Hence, to this end lasers may be applied, with relatively focused beams, to obtain the high resolution. As two-photon absorption is proportional to the square of the intensity, it only takes place while in focus providing high spatial resolution. Hence, the 3D printing stage may comprise exposing the resin to two-photon polymerization.

In embodiments, the device may be applied for microfluidic applications. In such embodiments, e.g. the interface element may comprise an inlet, and the cantilever may comprise, especially at a tip thereof, an outlet. The cantilever outlet may be in fluid communication with the inlet at the interface element via a microfluidic channel structure.

Therefore, in specific embodiments the device may comprise a microfluidic channel structure, wherein the microfluidic channel structure is at least partially comprised by the interface element, at least partially comprised by the cantilever support, and at least partially comprised by the (hollow) cantilever. Especially, the microfluidic channel structure comprises one or more channels. Therefore, the cantilever may be a hollow cantilever. The cantilever may comprise a channel having cross-sectional dimensions selected from the range of about 0.2-25 pm, such as selected from the range of about 0.5-15 pm, like in embodiments selected from the range of about 1-10 pm.

The cross-sectional channel dimensions of the microfluidic channel structure in the interface element may be in the order of about 0.2-500 pm.

The interface element may in embodiments comprise at least part of the microfluidic channel structure.

The interface element may comprise a first interface element opening and a second interface element opening, in fluidic contact with the first interface element opening. The second interface element opening may especially be comprised by the first face. The first interface element opening may especially be comprised by a side face of the interface element, though in general not the second face. However, other positions for the first interface element opening may also be possible.

The term “fluidic contact” may especially indicate that a fluid may flow between the elements which are indicated to be in fluidic contact. Especially, herein, a liquid, like water, may flow between the two elements.

In embodiments, the microfluidic channel structure may comprise a first opening and a second opening, wherein the first opening is arranged in the interface element, wherein the first opening is configured for fluidically coupling of the microfluidic channel structure to a fluid control system, and wherein the second opening is arranged in the cantilever. The second opening may especially be configured at the tip of the cantilever. The fluid control system may be external to the device, and may be functionally coupled to the device. The fluid control system may e.g. comprise a pump. Especially, the first interface element opening may comprise, or may be, the first opening.

Hence, the support structure may also comprise a channel or channel part. Therefore, in embodiments the support structure may be hollow. The channel or channel part comprised by the support structure may be indicated as support structure channel (part). At one end of the support structure channel, the support structure channel may be in fluidic contact with the second interface element opening and another end of the support channel may provide the cantilever support opening.

The interface element openings in the interface element may have dimensions similar to the cross-sectional dimensions of the microfluidic channel structure in the interface element, such as in the order of 0.2-500 pm. Hence, when the (relatively thin) reflective layer is provided to the first face, such as by sputtering, this opening may stay open. Further, the opening in the first face may facilitate alignment of the 3D printer for printing the cantilever support.

When the cantilever is hollow, also non-cured resin may have to be removed from the channel in the cantilever. Therefore, in embodiments the cantilever may comprise a hollow cantilever, and the method may comprise a resin removal stage comprising removing remaining resin from the hollow cantilever by flushing the hollow cantilever with a washing fluid. The washing fluid may comprise a solvent for the resin, or components thereof.

As indicated above, the (hollow) cantilever may comprise very thin 3D printed layers, such as having a thickness in the order of about 0.05-15 pm.

Further, as indicated above, the interface element may also be 3D printed. The 3D printed layers thereof may be thicker than that of the cantilever, as a high resolution may be less necessary for the interface element, than for the cantilever. Layer thicknesses (or height) may e.g. be in the order of 15-500 pm, such as selected from the range of 20-250 pm, like in embodiments selected from the range of about 20-200 pm, such as selected from the range of about 25-100 pm. In embodiments, the interface element may comprise a plurality of first 3D- printed layers, wherein the first 3D-printed layers comprise a first material selected from the group comprising cured photosensitive materials, and wherein the first 3D-printed layers have thicknesses independently selected from the range of 15-500 pm. Suitable photosensitive materials may comprise thiol-ene/yne photopolymerizable material. In embodiments, the photosensitive material may comprise material that is curable into acryl polymers or methacryl polymers. Further, the photosensitive material may comprise initiators, and optionally also additives, like TiCh. TiCh may increase the strength, and may e.g. increase Young’s modulus of the interface element. Hence, the first material may comprise a first additive selected from the group comprising TiCh and other UV absorbing (nano)particles or reflecting (nano)particles. In embodiments, the interface element may (also) be provided by one or more of stereolithography (SLA) or digital light processing (DLP).

As can be derived from the above, the cantilever may comprise a plurality of second 3D-printed layers, wherein the second 3D-printed layers may comprise a second material selected from the group comprising cured photosensitive materials. The second 3D- printed layers may have layer thicknesses independently selected from the range of 0.05-15 pm. Suitable photosensitive materials may also comprise thiol-ene/yne photopolymerizable material. In embodiments, the photosensitive material may comprise material that is curable into acryl polymers or methacryl polymers. Further, the photosensitive material may comprise initiators. In embodiments, the photosensitive material for the cantilever has no, or at least a lower amount of TiCh, or other (pigment) additives (such as UV absorbing (nano)particles or reflecting (nano)particles), than the interface element. In other embodiments, the photosensitive material for the cantilever may essentially have the same amount of TiCh, or other (pigment) additives (such as UV absorbing (nano)particles or reflecting (nano)particles) as the interface element. In embodiments, the cantilever may be provided by two-photon polymerization.

As can be derived from the above, the cantilever support may comprise a plurality of second 3D-printed layers, wherein the second 3D-printed layers may comprise a second material selected from the group comprising cured photosensitive materials. The second 3D-printed layers may have layer thicknesses independently selected from the range of 0.05- lS pm. Suitable photosensitive materials may also comprise thiol-ene/yne photopolymerizable material. In embodiments, the photosensitive material may comprise material that is curable into acryl polymers or methacryl polymers. Further, the photosensitive material may comprise initiators. In embodiments, the photosensitive material for the cantilever support has no, or at least a lower amount of TiCh, or other (pigment) additives, than the interface element. In other embodiments, the photosensitive material for the cantilever support may essentially have the same amount of TiCh, or other (pigment) additives (such as UV absorbing (nano)particles or reflecting (nano)particles) as the interface element. In embodiments, the cantilever support may be provided by using two-photon polymerization.

Herein, the term “cured photosensitive” material may refer to 3D printed material. The 3D printed material may comprise in embodiments cured acryl polymers and/or cured methacryl polymers. Hence, the first material may comprise cured acryl polymers and/or cured methacryl polymers. Hence, the second material may comprise cured acryl polymers and/or cured methacryl polymers. The first material and the second material may be the same materials or may be different material. In specific embodiments, they may essentially have the same composition. In other embodiments, the compositions may differ, e.g. with respect to additive material and/or additive amount.

The phrase “thicknesses independently selected from”, and similar phrases, may indicate that in embodiments different layers may have different thicknesses but may also indicate that in (other) embodiments two or more layers may have the same thicknesses.

Instead of the terms “layer thickness” or “thickness”, also the term height may be applied.

The layer widths may in embodiments be in the order of the layer thicknesses or larger. Hence, the layer widths may be selected from the range of 75-500% of the respective layer heights, such as selected from the range of 100-400% of the layer thickness (i.e. 1-4 times the thickness).

In embodiments, the 3D printed material of the cantilever has no, or at least a lower amount of TiCh, or of other (pigment) additives (such as UV absorbing (nano)particles or reflecting (nano)particles), than the interface element. In other embodiments, the 3D printed material of the cantilever may essentially have the same amount of TiCh, or other (pigment) additives (such as UV absorbing (nano)particles or reflecting (nano)particles) as the interface element.

Hence, herein the term “3D printable material”, and similar terms, may refer to uncured material and the term “3D printed material”, and similar terms, may refer to the cured (3D printable) material. In embodiments, the former may e.g. comprise one or more of acrylatemethacrylate monomers and acrylate-methacrylate oligomers, and the latter may comprise acrylate-methacrylate polymers. In embodiments, the former may e.g. comprise thiol-ene/yne photopolymerizable material, and the latter may comprise acryl polymers and/or methacryl polymers.

For protecting the cantilever, the second face may comprise a protruding element which may facilitate that a body touching the device from one or more directions, may not immediately touch the cantilever. In particular, the device may comprise at least one, especially at least two, protruding elements protruding from the second face and configured to protect the cantilever. Therefore, in embodiments the cantilever may be arranged adjacent to two or more protruding elements protruding from the second face, wherein the protruding elements protrude further from the second face than the cantilever. A shortest distance between a protruding element and the cantilever may be selected from the range of 20-2000 pm, such as 100-200 pm. Seen e.g. in top view, the cantilever may be configured between two protruding elements. In specific embodiments, the protruding elements protrude further away relative to the second face than the cantilever may protrude relative to the second face.

The invention may further comprise providing the cantilever with a tip at one end of the cantilever, wherein the tip has a tip axis that is non-perpendicular to the axis of elongation. For instance, an angle between the tip axis and the axis of elongation may be selected from the range of 95-135°, such as selected from the range of 105-135°. The tip may have a shape approximating a cone or a pyramid, especially in embodiments a cone. Hence, in embodiments the tip may have a conical or pyramidal shape, especially conical.

Further, in embodiments the tip may (even) protrude beyond the cantilever. A distance with which the tip may protrude relative to the cantilever may in embodiments be selected from the range of 1-10% of the total length of the cantilever and/or in embodiments be selected from the range of 5-50 pm.

Especially, the tip is of the same material as the cantilever and made via the same type of process (especially two-photon polymerization (2PP)).

When the cantilever has been printed, and preferably the non-cure resin (has been) removed, the device may be removed from the breakout beams. Hence, in embodiments the method may comprise a separation stage comprising separating the main body (with the cantilever) from the support structure, especially by breaking the breakout beams.

In yet a further aspect, the invention also provides a device as such. Therefore, in embodiments the invention also provides a device obtainable with the method as described herein.

Especially, the device may comprise a main body, wherein the main body comprises the cantilever support and the (planar) interface element, wherein the interface element comprises the first face and the second face (different from the first face)), wherein the cantilever support is arranged on the first face, wherein the device further comprises the cantilever, functionally coupled to the cantilever support, and extending therefrom.

For further embodiments of the device, it is further referred to the above described embodiments in relation to the method.

In specific embodiments, the reflective layer may be arranged on at least part of the first face, wherein between the first face and the cantilever support, at least part of the reflective layer is disrupted. Further, in embodiments the device may comprise the microfluidic channel structure (as described above).

In embodiments, the cantilever support may be stereolithography (SLA) or digital light processing (DLP) produced cantilever support. In embodiments, the cantilever may be a 2-photon polymerization produced cantilever.

As indicated above, a reflective element may be configured on the first face of the interface element. However, between the first face and the cantilever support, at least part of the reflective layer may be disrupted.

The cantilever may comprise cantilever sections, wherein the cantilever sections are arranged at (respective) angles a _c to an axis of elongation of the cantilever, wherein the angles a _c are (independently) selected from the range of 30° - 60°. Yet further, in specific embodiments the cantilever sections may have (respective) length(s) L _s along the axis of elongation, wherein the length(s) L _s is (are) selected from the range of 0.05-15 pm, more especially 0.05-12 pm, such as about 0.1-10 pm, like more especially selected from the range of 0.5-10 pm, such as selected from the range of 2-6 pm.

In embodiments, the cantilever may comprise a plurality of second 3D-printed layers. The second 3D-printed layers may comprise a second material selected from the group comprising cured photosensitive materials. The second 3D-printed layers may have thicknesses independently selected from the range of 0.05-15 pm.

In embodiments, the cantilever support may comprise a plurality of second 3D- printed layers, wherein the second 3D-printed layers may comprise a second material selected from the group comprising cured photosensitive materials. The second 3D-printed layers may have thicknesses independently selected from the range of 0.05-15 pm.

In embodiments, the interface element may comprise a plurality of first 3D- printed layers, wherein the first 3D-printed layers comprise a first material selected from the group comprising cured photosensitive materials. The first 3D-printed layers may have thicknesses independently selected from the range of 15-500 pm.

The first material may comprise acrylate-methacrylate polymers. In embodiments, the first material may comprise acryl polymers and/or methacryl polymers. The second material may comprise acrylate-methacrylate polymers. In embodiments, the second material may comprise acryl polymers and/or methacryl polymers.

In yet a further aspect, the invention also provides a 3D printer suitable for 3D printing the cantilever. Especially, the invention provides in embodiments a 3D-printer for 3D-printing a device comprising a cantilever. Especially, the 3D-printer comprises a device control system, a radiation source, a printing site, and a resin control system. In embodiments, the printing site may comprise a support structure. Further, the printing site may especially be configured for receiving a main body in a first configuration (or “first arrangement”). The main body may comprise a cantilever support and an interface element. Especially, the cantilever support is arranged on a first face of the interface element. In embodiments, in the first configuration a second face (different from the first face) of the interface element may be arranged at a first distance (dl) from a support structure. Especially, the first distance (dl) may be selected from the range of 50 - 500 pm. Especially, the device control system may be configured to execute an operational mode, wherein the operational mode comprises: (a) a resin providing stage comprising the resin control system providing a droplet at least partially onto the first face and at least partially onto the support structure, wherein the droplet comprises a photosensitive (liquid) resin configured to cure when exposed to first radiation; and (b) a 3D printing stage comprising the radiation source providing first radiation to the resin in order to generate the cantilever, wherein the cantilever protrudes from the cantilever support and beyond the second face. Hence, especially in embodiments the invention provides a 3D-printer for 3D-printing a device comprising a cantilever, wherein the 3D-printer comprises a device control system, a radiation source, a printing site, and a resin control system, wherein the printing site comprises a support structure, and wherein the printing site is configured for receiving a main body in a first configuration, wherein the main body comprises a cantilever support and an interface element, wherein the cantilever support is arranged on a first face of the interface element, and wherein in the first configuration a second face of the interface element is arranged at a first distance (dl) from a support structure, wherein the first distance (dl) is selected from the range of 50 - 500 pm, and wherein the device control system is configured to execute an operational mode, wherein the operational mode comprises: (a) a resin providing stage comprising the resin control system providing a droplet at least partially onto the first face and at least partially onto the support structure, wherein the droplet comprises a photosensitive (liquid) resin configured to cure when exposed to first radiation; and (b) a 3D printing stage comprising the radiation source providing first radiation to the resin in order to generate the cantilever, wherein the cantilever protrudes from the cantilever support and beyond the second face. In specific embodiments, the 3D-printer may be configured to execute the method of the invention as described herein. In yet a further aspect, the invention provides a data carrier carrying thereupon program instructions which, when executed by a control system functionally coupled to a 3D- printer, cause the 3D-printer to carry out the method as described herein.

In yet a further aspect, the invention also provides a computer program product comprising program instructions for execution on a control system functionally coupled to a 3D-printer, wherein the program instructions, when executed by the control system, cause the 3D-printer to carry out the method as described herein.

In yet a further aspect, the invention also provides a method for operating the device, especially comprising the microfluidic channel structure, wherein the method comprises one or more of: (i) providing a fluid through the second opening in the cantilever; (ii) providing suction at the second opening of the cantilever. Further, in specific embodiments such method may comprise applying a modulation to a cell with the cantilever, wherein the modulation comprises one or more of: (a) picking up a cell with the cantilever; (b) adhering the cantilever to a cell; (c) delivering fluid onto a cell with the cantilever; and (d) injecting fluid into a cell with the cantilever.

The term “controlling” and similar terms especially refer at least to determining the behavior or supervising the running of an element. Hence, herein “controlling” and similar terms may e.g. refer to imposing behavior to the element (determining the behavior or supervising the running of an element), etc., such as e.g. measuring, displaying, actuating, opening, shifting, changing temperature, etc.. Beyond that, the term “controlling” and similar terms may additionally include monitoring. Hence, the term “controlling” and similar terms may include imposing behavior on an element and also imposing behavior on an element and monitoring the element. The controlling of the element can be done with a control system, which may also be indicated as “controller”. The control system and the element may thus at least temporarily, or permanently, functionally be coupled. The element may comprise the control system. In embodiments, the control system and element may not be physically coupled. Control can be done via wired and/or wireless control. The term “control system” may also refer to a plurality of different control systems, which especially are functionally coupled, and of which e.g. one control system may be a master control system and one or more others may be slave control systems. A control system may comprise or may be functionally coupled to a user interface.

The control system may also be configured to receive and execute instructions from a remote control. In embodiments, the control system may be controlled via an App on a device, such as a portable device, like a Smartphone or I-phone, a tablet, etc.. The device is thus not necessarily coupled to the lighting system, but may be (temporarily) functionally coupled to the lighting system.

Hence, in embodiments the control system may (also) be configured to be controlled by an App on a remote device. In such embodiments the control system of the lighting system may be a slave control system or control in a slave mode. For instance, the lighting system may be identifiable with a code, especially a unique code for the respective lighting system. The control system of the lighting system may be configured to be controlled by an external control system which has access to the lighting system on the basis of knowledge (input by a user interface of with an optical sensor (e.g. QR code reader) of the (unique) code. The lighting system may also comprise means for communicating with other systems or devices, such as on the basis of Bluetooth, WIFI, LiFi, ZigBee, BLE or WiMAX, or another wireless technology.

The system, or apparatus, or device may execute an action in a “mode” or “operation mode” or “mode of operation” or “operational mode”. The term “operational mode may also be indicated as “controlling mode”. Likewise, in a method an action or stage, or step may be executed in a “mode” or “operation mode” or “mode of operation” or “operational mode”. This does not exclude that the system, or apparatus, or device may also be adapted for providing another controlling mode, or a plurality of other controlling modes. Likewise, this may not exclude that before executing the mode and/or after executing the mode one or more other modes may be executed.

However, in embodiments a control system may be available, that is adapted to provide at least the controlling mode. Would other modes be available, the choice of such modes may especially be executed via a user interface, though other options, like executing a mode in dependence of a sensor signal or a (time) scheme, may also be possible. The operation mode may in embodiments also refer to a system, or apparatus, or device, that can only operate in a single operation mode (i.e. “on”, without further tunability).

Hence, in embodiments, the control system may control in dependence of one or more of an input signal of a user interface, a sensor signal (of a sensor), and a timer. The term “timer” may refer to a clock and/or a predetermined time scheme.

The invention also provides a method for 3D-printing a device comprising a suspended structure, such as a cantilever, wherein the method comprises: a preparation stage comprising providing a main body, wherein the main body comprises (i) an interface element and (ii) one or more suspended structure supports; wherein the interface element comprises a first face, wherein the one or more suspended structure supports are arranged on the first face; a resin providing stage comprising providing a droplet (at least partially) onto the first face, wherein the droplet comprises a photosensitive resin configured to cure when exposed to first radiation; a 3D printing stage comprising generating the suspended structure by exposing the resin to first radiation, wherein the suspended structure bridges a distance between at least two suspended structure supports.

The term “stage” and similar terms used herein may refer to a (time) period (also “phase”) of a method and/or an operational mode. The different stages may (partially) overlap (in time). However, generally, the stages may be executed sequentially. For instance, in embodiments, the preparation stage may be finished prior to starting the resin providing stage, which may be finished prior to starting the 3D printing stage.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments of the invention will now be described, by way of example only, with reference to the accompanying schematic drawings in which corresponding reference symbols indicate corresponding parts, and in which: Figs, la-lg schematically depict an embodiment of the method for 3D printing a device as well as embodiments of the device, and also an embodiment of the 3D printer; and Fig. 2 shows some cantilever and tip embodiments. The schematic drawings are not necessarily to scale.

DETAILED DESCRIPTION OF THE EMBODIMENTS

Materials & methods

Similar methods as described in Robert C.L.N. Kramer et al. in Lab Chip, 2020, 20, 311, DOI: 10.1039/c91c00668k were used herein. This paper is herein incorporated by reference. The below part of the materials & method passage substantially overlaps with, but is not fully identical to passages from this paper:

The printing of the microfluidic AFM cantilever probe was done in two parts: an interface part and a cantilever part. The fluidic interface was the connection between the hollow cantilever and the “external -world”. This interface part was printed with the SL method and the cantilever part was printed on top of this interface with the 2PP method. (Note that interface could be also made out of glass-based materials or silicon-based materials fabricated by printing or cleanroom fabrication methods.) Stereolithography (SL of SLA): The SL method is based on spatially controlled layer-by-layer solidification of a liquid resin by photopolymerization. A commercial desktop SL printer (Micro® Plus Hi-Res, EnvisionTEC GmbH) and a methacrylate/ acrylate-based resin (E.g. HTM140V2M, 3DM etc) were used. The highest printing resolution depends on the printing direction and a resolution of 25 pm in the z-direction (perpendicular to the build plate) and a minimum channel opening size of 150 pm x 90 pm in the xy -plane were obtained. Other 3D resin printers can also can be used.

The fluidic interface part was printed using standard system settings. The dimensions of the interface were chosen such that it fits in the AFM holder. After printing, all unwanted resin residues were removed from inside and outside the channel by blowing compressed air and two minutes of ultrasonic cleaning in isopropyl alcohol (IP A). Tygon® (ID 190.5 pm, OD 2 mm) tubing from Cole-Palmer was used as a connection to the fluidic interface from the “external world”.

Two-photon polymerization (2PP): The 2PP method is also a spatially controlled layer-by-layer solidification process of a photosensitive liquid resin by almost simultaneous non-linear absorption of ultrashort laser pulses. With this method, feature sizes of less than 100 nm can be printed. A photonic professional GT printer and a carbamate/methacrylate-based compound (IP-S) photoresist with a material density of 1.2 g cm-3 from Nanoscribe GmbH were used.

To print the cantilever, the SL-printed interface was taped on an indium -tinoxide (ITO) coated glass slide and mounted in the 2PP -printer. Then, a drop of resist was placed covering the area where polymerization was desired including the surrounding glass surface. The 2PP system can automatically find the smooth ITO interface on the glass surface. However, the surface of the SL-printed part was not smooth and it was therefore difficult to automatically identify its surface. Determining the surface height of the SL-printed surface was crucial to get a good seal between the SL-printed polymer and 2PP printed polymer. To enable automatic identification of the SL-printed surface, an optimized thin-film reflective coating was deposited. All the optimized parameters used for printing are given in the table below.

2PP printing was done in four different parts connected with each other: a structured base, dome, hollow cantilever, and tip (with or without an aperture). A structured base with a large surface area was chosen to be printed on the SL-printed part. This base structure was crucial to get a good seal between the two polymers of both printing methods. On this base, a dome shape (such as e.g. a yurt-shape) structure was printed. This particular shape was chosen to reduce the printing time, as compared to a dome. The hollow cantilever was then printed attached to this yurt as a series of overlapping vertical square slices positioned at an angle. Finally, the desired tip shape was printed.

The printed devices were tested for their mechanical characteristics and their functionality with cells.

Device characterization: The printed devices were imaged with an optical microscope (Keyence Digital Microscope VHX-6000) and sputter-coated with a reflective thin- film of gold/ palladium layer of 18 nm for imaging with a scanning electron microscope (SEM) (JSM-6010LA, Jeol). The cantilever was mechanically characterized for its resonance frequency by laser Doppler vibrometry (LDV) (MSA400 Micro System Analyser, Polytec GmbH). This laser beam was focused near the tip at the free end of the cantilever, where the amplitude of vibration was maximum. The sputter-coated gold/palladium layer enhanced the laser beam reflection of the LDV from the cantilever polymeric material surface. The printed device was mounted on a PZT piezoelectric element that was actuated by a pseudo-random signal with an amplitude of 5 volts over a frequency bandwidth from 50 kHz to 200 kHz.

Further description of detailed embodiments

Fig. la schematically depicts an embodiment of the method for 3D printing a device 100 as well as an embodiment of the device as such, as well as an embodiment of the 3D printer. Fig. la schematically depicts the method with the device in top views in different stages. Figs, lb schematically depicts at least part of the method with the device in sideview (or cross-sectional view). Fig. 1c schematically depicts an embodiment of the interface element. Fig. Id schematically depicts an embodiment of the device.

Referring to Figs, la-lb, the invention provides a method for 3D-printing a device 100 comprising a cantilever 150. The method may comprise a preparation stage comprising providing (i) a main body 120, and (ii) a support structure 210. The main body 120 may comprise a cantilever support 130 and an (planar) interface element 110. The interface element 110 may comprise a first face 111 and a second face 112 (different from the first face). The cantilever support 130 may be arranged on the first face 111. The support structure 210 may be configured at a first distance dl from the second face 112. The first distance dl may be selected from the range of 50 - 500 pm. Planes defined by the first face 111 and the second face 112 may be arranged at an angle selected from the range of 60 - 120°.

The method may comprise a resin providing stage comprising providing a droplet 20 at least partially onto the first face 111 and at least partially onto the support structure 210 (see also stage IV in Fig. la). The droplet 20 may comprise a photosensitive (liquid) resin configured to cure when exposed to first radiation 11. The photosensitive resin may have a high viscosity at room temperature, such as at least about 100 mPa s, more especially at least about 200 mPa s, such as at least about 500 mPa s, such as in embodiment at least about 1000 mPa s. The viscosity may be up to about 1.10 ⁵ mPa- s, such as up to about 5.10 ⁴ mPa- s.

Further, the method may comprise a 3D printing stage comprising generating the cantilever 150 by exposing the resin to first radiation 11, see stage V in Fig. la and see Fig. lb. The cantilever 150 protrudes from the cantilever support 130 and beyond the second face 112.

In embodiments, the preparation stage may comprise an interface providing substage comprising providing the interface element 110. Further, the preparation stage may comprise a cantilever support providing substage comprising arranging the cantilever support 130 on the first face 111 of the interface element 110, see also phase I in Fig. la.

In embodiments, (see also Fig. lb), the cantilever support 130 has a dome-like shape.

In embodiments, see also phases III and IV of Fig. la, the cantilever support providing substage may comprise providing the cantilever support 130 with a cantilever support opening 131. Referring to stage V, or more precisely the time period between stage VI and V, the 3D printing stage may comprise generating the cantilever from the cantilever support opening 131.

Referring to Fig. 1c, in embodiments the interface providing substage may comprise arranging a reflective element 115 on the first face 111. Hence, stage I in Fig. la may also start with an interface element 110 including the reflective element 115 as schematically depicted in Fig. 1c. Therefore, the cantilever support providing substage may comprise locating the reflective element 115 and positioning the cantilever support 130 based on the location of the reflective element 115. The reflective element 115 may comprise a metal selected from the group comprising gold, silver, aluminum, and titanium. Further, in embodiments the reflective element 115 may comprise a reflective layer 116 having a thickness d2 selected from the range of 1-5 nm. With the thin reflective element the 3D printer may more easily find the interface element by an optical method using reflection from surfaces. The higher the surface reflection, the higher the probability of finding the surface, and thus the place where 3D printing can be executed. Otherwise, the cantilever support, which may especially be dome-shaped, may not be positioned properly on the interface surface and the sealing between the dome and the interface may have a lower quality than desired.

Due to the two-photon process that may also be used for generating the (domeshaped) cantilever support 130, the relatively thin reflective element may be disrupted due to the relatively high intensity light 11 provided. As schematically depicted in Fig. Id, between the first face 111 and the cantilever support 130, at least part of the reflective layer 116 may be disrupted. In Fig. Id, reference A indicates an axis of elongation of the cantilever 150. The axis of elongation may be arranged parallel to the first face 111.

Referring to Fig. lb, the preparation stage may comprise providing the main body 120 connected to a main body holder 200 via (3D printed) breakout beams 201.

Further, the second face 112 and the support structure 210 are separated by a gap 205 providing the first distance dl. Especially, in embodiments the cantilever 160 may bridge the gap 205. The cantilever 150 has a cantilever length L (along an axis of elongation of the cantilever). The cantilever length L may in embodiments be at least 250 pm.

The 3D printing stage may comprise exposing the resin to two-photon polymerization. This may not only apply for the 3D printing stage of the cantilever 150, but may also apply to a 3D printing of the cantilever support 130.

Referring to the dashed line in the embodiment of stage VI of Fig. la and to Figs. Ic-ld, the device 100 may comprise a microfluidic channel structure 170. The microfluidic channel structure 170 may be at least partially comprised by the interface element 110, at least partially comprised by the cantilever support 130, and at least partially comprised by the cantilever 150. The microfluidic channel structure 170 may comprise one or more channels 175. The microfluidic channel structure 170 may comprise a first opening 171 and a second opening 172. The first opening 171 may be arranged in the interface element 110. The first opening 171 may be configured for fluidically coupling of the microfluidic channel structure 170 to a fluid control system 350. The fluid control system 350 may comprise a pump. The second opening 172 may be arranged in the cantilever 150, especially at the tip of the cantilever. The channel or channel part comprised by the support structure may be indicated as support structure channel (part). The support structure channel may thus be comprised by the microfluidic channel structure 170. The support structure channel may provide a fluidic coupling between the hollow cantilever 50 and the interface element 110 comprising at least part of the microfluidic channel structure 170. Hence, the cantilever support opening 131 may be in fluidic contact with the first opening 171 and the second opening 172.

The interface element 110 may comprise a first interface element opening 173 and a second interface element opening 174, in fluidic contact with the first interface element opening 173. They may be connected via a channel 175. Especially, the first interface element opening 173 may comprise, or may be, the first opening 171. The latter may e.g. be functionally coupled to a pump.

Hence, especially the cantilever 150 may comprise a hollow cantilever 50. Hence, the method may also comprise a resin removal stage comprising removing remaining resin from the hollow cantilever 50 by flushing the hollow cantilever 50 with a washing fluid.

As schematically depicted, the cantilever 150 may be arranged adjacent to two or more protruding elements 181 protruding from the second face 112. In top view, the cantilever 150 may be configured between two protruding elements 181. A third distance d3, being the shortest distance between the protruding element(s) 181 and the cantilever 150, may be selected from the range 20-2000 pm, such as 100-200 pm. In embodiments, the protruding elements 181 protrude further from the second face 112 than the cantilever 150.

After the cantilever 150 has been 3D printed, remaining resin may be removed. Hence, the method may comprise a resin removal stage comprising removing remaining resin from the hollow cantilever (50) by flushing the (hollow) cantilever (50) with a washing fluid. Further, the method may comprise a separation stage comprising separating the main body 120 (with the cantilever) from the support structure 210, especially by breaking the breakout beams 201.

Figs, le-lf schematically depict some further aspects. Fig. le very schematically depicts part of the interface element 110, showing the dimensional differences between the 3D printed material of the interface element 110 and of the cantilever support 130 very schematically. Reference i may indicate interface element edges. The interface element 110 may comprise a plurality of first 3D-printed layers 132. The first 3D-printed layers 132 comprise a first material selected from the group comprising cured photosensitive materials. The first 3D-printed layers 132 have thicknesses independently selected from the range of 15- 500 pm. This thickness is indicated in Fig. le with reference hl. For instance, the curable photosensitive material may comprise 3DM from Admat. 3DM from Admat comprises acrylate-methacrylate monomers, acrylate-methacrylate oligomers and photo initiators. The first material may comprise a first additive selected from the group comprising TiCh.

The cantilever (not depicted) and the cantilever support 130 may comprise a plurality of second 3D-printed layers 232. The second 3D-printed layers 232 comprise a second material selected from the group comprising cured photosensitive materials. The second 3D- printed layers 232 may have thicknesses independently selected from the range of 0.05-15 pm. This thickness is indicated in Fig. le with reference h2. Hence, the cantilever and the cantilever support may comprise the second material.

Referring to Fig. If, the cantilever support providing substage may comprise providing a plurality of hexagonal support sections 137 to provide the cantilever support 130. The support sections 137 are made from the second material and allow a faster 3D printing of the cantilever support and/or lead to a more robust cantilever support.

Here, the cantilever support 130 is shown with the cantilever support opening 131. The cantilever may be generated from the cantilever support 130, and the hollow cantilever may be generated from the support opening 131. Anyhow, the hollow cantilever may be functionally coupled to the cantilever support opening 131.

Fig. 1g schematically depicts a cantilever 150, which may be the result of a 3D printing stage which comprises sequentially generating cantilever sections 152 of the cantilever from the cantilever support 130. The cantilever sections 152 are arranged at (respective) angles etc to an axis of elongation A of the cantilever 150. The angles a _c may independently be selected from the range of 30° - 60°. The cantilever sections 152 have (respective) lengths L _s along the axis of elongation. The length L _s may be selected from the range of 2 - 6 pm. The cantilever sections may comprise the second material.

Referring further to Fig. lb, the invention also provides a 3D-printer 1000 for 3D-printing a device 100 comprising a cantilever 150. The 3D-printer 1000 may comprise a device control system 300 or may be functionally coupled to such device control system 300. The 3D printer 1000 may comprise a radiation source 10, and a printing site 1010. The 3D printer 1000 may in embodiments comprise a resin control system 1020. The printing site 1010 may - during operation of the 3D printer 1000 - comprise a support structure 210. The printing site 1010 may be configured for receiving a main body 120 in a first configuration. The main body 120 may comprise a cantilever support 130 and an interface element 110. The cantilever support 130 may be arranged on a first face 111 of the interface element 110. In the first configuration a second face 112 (different from the first face 111) of the interface element 110 may be arranged at a first distance dl from a support structure 210. The first distance dl may be selected from the range of 50 - 500 pm. The device control system 300 may be configured to execute an operational mode. The operational mode may comprise: (a) a resin providing stage comprising the resin control system 1020 providing a droplet 20 at least partially onto the first face 111 and at least partially onto the support structure 210. The droplet 20 may comprise a photosensitive (liquid) resin configured to cure when exposed to first radiation 11. The operational mode may comprise: (b) a 3D printing stage comprising the radiation source 10 providing first radiation 11 to the resin in order to generate the cantilever 150. The cantilever 150 protrudes from the cantilever support 130 and beyond the second face 112. The resin control system 1020 may be configured to provide the droplet 20 to the cantilever support and support structure 210. The 3D-printer 1000 may be configured to execute the method of the invention. Hence, in an operational mode of the 3D-printer 1000, the 3D-printer 1000 executes the method of the invention as described herein.

The invention also provides a data carrier carrying thereupon program instructions which, when executed by a control system 305 functionally coupled to a 3D-printer 1000, cause the 3D-printer 1000 to carry out the method as described herein. The control system 305 may be comprised by the device control system 300. The invention also provides a computer program product comprising program instructions for execution on a control system 305 functionally coupled to a 3D-printer 1000. The program instructions, when executed by the control system 305, may cause the 3D-printer 1000 to carry out the method of the invention.

Fig. la and Id also schematically depict embodiments of the device 100 as such. Hence, a device 100 obtainable with the method as described herein is also provided.

In embodiments of the device 100, a reflective layer 116 may be arranged on the first face 111. Between the first face 111 and the cantilever support 130, at least part of the reflective layer 116 may be disrupted. The device 100 may comprise a microfluidic channel structure 170.

The invention allows, amongst others, a method for operating the device 100, comprising one or more of: (i) providing a fluid through the second opening 172 in the cantilever 150; and (ii) providing suction at the second opening 172 of the cantilever 150. The method may comprise applying a modulation to a cell with the cantilever 150; the modulation may comprise one or more of: (a) picking up a cell with the cantilever 150; (b) adhering the cantilever 150 to a cell; (c) delivering fluid onto a cell with the cantilever 150; and (d) injecting fluid into a cell with the cantilever 150. Fig. 2 schematically depicts some embodiments of the cantilever 150, especially a hollow cantilever. The second opening 172 of the channel structure may especially be configured at a tip, which tip may extend from the cantilever. Hence. The cantilever may comprise an elongated structure, with the axis of elongation, and the tip may extend therefrom (protrude therefrom). Hence, an axis of the tip (“tip axis”) may be configured under an angle with the axis of elongation. In Fig. 2, left top, the angle is indicated as angle with a normal to the axis of elongation. Relative to the axis of elongation, an angle between the tip axis and the axis of elongation may be selected from the range of 95-135°, such as selected from the range of 105-135°. Relative to the cantilever support, the tip may point away from the cantilever support. The tip may even protrude beyond the cantilever 150. This is indicated with distance d4. This distance d4 may in embodiments be selected from the range of 1-10% of the total length of the cantilever. Alternatively or additionally, the distance d4 may in embodiments be selected from the range of 5-50 pm. Hence, the tip may be in a kind of overhang configuration relative to the cantilever 150, like the cantilever 150 may be configured in a kind of overhang configuration relative to the interface element.

The term “plurality” refers to two or more.

The terms “substantially” or “essentially” herein, and similar terms, will be understood by the person skilled in the art. The terms “substantially” or “essentially” may also include embodiments with “entirely”, “completely”, “all”, etc. Hence, in embodiments the adjective substantially or essentially may also be removed. Where applicable, the term “substantially” or the term “essentially” may also relate to 90% or higher, such as 95% or higher, especially 99% or higher, even more especially 99.5% or higher, including 100%.

The term “comprise” also includes embodiments wherein the term “comprises” means “consists of’.

The term “and/or” especially relates to one or more of the items mentioned before and after “and/or”. For instance, a phrase “item 1 and/or item 2” and similar phrases may relate to one or more of item 1 and item 2. The term "comprising" may in an embodiment refer to "consisting of' but may in another embodiment also refer to "containing at least the defined species and optionally one or more other species".

Furthermore, the terms first, second, third and the like in the description and in the claims, are used for distinguishing between similar elements and not necessarily for describing a sequential or chronological order. It is to be understood that the terms so used are interchangeable under appropriate circumstances and that the embodiments of the invention described herein are capable of operation in other sequences than described or illustrated herein. The devices, apparatus, or systems may herein amongst others be described during operation. As will be clear to the person skilled in the art, the invention is not limited to methods of operation, or devices, apparatus, or systems in operation.

It should be noted that the above-mentioned embodiments illustrate rather than limit the invention, and that those skilled in the art will be able to design many alternative embodiments without departing from the scope of the appended claims.

In the claims, any reference signs placed between parentheses shall not be construed as limiting the claim.

Use of the verb "to comprise" and its conjugations does not exclude the presence of elements or steps other than those stated in a claim. Unless the context clearly requires otherwise, throughout the description and the claims, the words “comprise”, “comprising”, and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in the sense of “including, but not limited to”.

The article "a" or "an" preceding an element does not exclude the presence of a plurality of such elements.

The invention may be implemented by means of hardware comprising several distinct elements, and by means of a suitably programmed computer. In a device claim, or an apparatus claim, or a system claim, enumerating several means, several of these means may be embodied by one and the same item of hardware. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage. In yet a further aspect, the invention (thus) provides a software product, which, when running on a computer is capable of bringing about (one or more embodiments of) the method as described herein.

The invention also provides a control system that may control the device, apparatus, or system, or that may execute the herein described method or process. Yet further, the invention also provides a computer program product, when running on a computer which is functionally coupled to or comprised by the device, apparatus, or system, controls one or more controllable elements of such device, apparatus, or system.

The invention further applies to a device, apparatus, or system comprising one or more of the characterizing features described in the description and/or shown in the attached drawings. The invention further pertains to a method or process comprising one or more of the characterizing features described in the description and/or shown in the attached drawings.

The various aspects discussed in this patent can be combined in order to provide additional advantages. Further, the person skilled in the art will understand that embodiments can be combined, and that also more than two embodiments can be combined. Furthermore, some of the features can form the basis for one or more divisional applications.

Relative to prior art solution, the present devices may have higher resolution, may have smoother surfaces, and may have smaller apertures. The tip shapes may be different, and may e.g. be bent away from the cantilever, allowing better vision.

The present device may e.g. be used for one or more of dip pen nanolithography, nanoscale dispensing, as nano fountain probe, scanning ion pipette, dispensing probe, scanning ion conductance microscope, as bio plume, or as aspirating micro/nano pipette.