Microstructure and method for capturing and manipulating a target in a fluid medium

Abstract

A microstructure (10) for capturing and manipulating a target (18), such as a motile target, in a fluid medium, the microstructure (10) comprising at least one chamber (12) provided with an entrance (14), wherein a cross-section of the entrance (14) is smaller than a cross-section of the chamber (12). A method for capturing and manipulating a target (18), such as a motile target, in a fluid medium, comprising: - capturing the target (18) in a chamber (12) of a microstructure (10); - moving the microstructure (10) enclosing the target (18); - releasing the target (18) by moving the microstructure (10) around the target (18) so as to extract the target from the chamber (12).

Description

Microstructure and method for capturing and manipulating a target in a fluid mediumTECHNICAL FIELD

[0001] The present disclosure relates to the field of manipulation of microorganisms or biological cells, and more particularly to a microstructure and method for capturing and manipulating a target, such as a motile target, in a fluid medium.TECHNOLOGICAL BACKGROUND

[0002] Manipulation of microorganisms or biological cells, e.g. single-cells or more specifically spermatozoa, in a fluid medium, is commonly achieved by micromanipulation systems using pipettes, i.e. macro-scale actuators that precisely position a glass pipette, and only the pipette tip is micrometer-sized. This pipette-based manipulation does not allow cell handling in confined environments such as microfluidic chips.

[0003] To overcome these shortcomings, remote manipulation has been considered in studies such as Xu, Haifeng, et al. "Sperm-hybrid micromotor for targeted drug delivery." ACS nano 12.1 (2018): 327-337, which discloses an articulated structure for capturing a sperm between four arms and releasing it by moving the arms when they reach their destination. However, such a structure is relatively difficult to manufacture and the movable arms make the releasing process possibly unreliable.

[0004] Therefore, there is a need for a new type of microstructure for capturing and manipulating a target.SUMMARY

[0005] In this respect, the present disclosure relates to a microstructure for capturing and manipulating a target in a fluid medium, the microstructure comprising at least one chamber provided with anentrance, wherein a cross-section of the entrance is smaller than a crosssection of the chamber.

[0006] The target may be any type of object, e.g. motile or immobile, that it is desired to manipulate. The target may be a microorganism, a single cell, a group of cells (e.g. cells attached to one another), a particle or the like. The target may be already present in the fluid medium, and capturing it by the microstructure enables to manipulate the target indirectly by manipulating the microstructure.

[0007] Thanks to its ability to be manipulated, e.g. moved within the fluid medium, the microstructure may be referred to as a microrobot, although it may not have the features that macroscopic robots usually have (e.g. processor-based control, articulated parts, etc.). As its name suggests, the microstructure may have dimensions less than 1 millimeter (mm), preferably less than 0.5 mm, preferably less than 300 micrometer (pm), preferably less than 100 pm.

[0008] The microstructure comprises at least one chamber. As used herein, for conciseness and unless the context indicates otherwise, "a", "an", and "the" are intended to refer to "at least one" or "each" and to include plural forms as well. Conversely, generic uses of the plural form may include singular elements.

[0009] The chamber may be sized for accommodating at least part of the target, specifically a part of the target that is big enough for manipulating the target through manipulation of the microstructure. For instance, for microorganisms or cells having a flagella (e.g. flagellated algae or spermatozoa), said part of the target may be the target's head, without the flagella, and the chamber may be sized to receive the head while the flagella may remain outside the chamber.

[0010] The chamber is provided with an entrance through which the target can at least partially enter the chamber. The entrance may be embodied as an opening in a wall of the chamber.

[0011] As defined above, a cross-section of the entrance is smaller than a cross-section of the chamber. For instance, the width and / or the height of the entrance may be less than the width and / or the height of the chamber, respectively.

[0012] Thanks to the above-defined chamber and entrance, the proposed microstructure enables capturing a target into the chamber. Once the target is at least partially inside the chamber, the entrance being smaller in cross-section ensures that it is difficult for the target to accidentally exit the chamber. Therefore, the target, even if it is a motile target, can be manipulated, e.g. moved within the fluid medium, efficiently and reliably although the microstructure remains simple. Releasing the target may be achieved by moving the microstructure around the target so as to extract the target from the chamber, e.g. through the entrance.

[0013] Optionally, a cross-section of the chamber is less than or as large as three times the cross-section of the entrance, optionally less than or as large as twice the cross-section of the entrance. This ratio may apply to the width and / or the height of the entrance and the chamber, respectively. Owing to these ratios, the chamber is not excessively large as compared to the entrance. This ensures that the target is not enabled to move too much inside the chamber, as enabling large movements of the target inside the chamber might help it to accidentally find its way out.

[0014] Optionally, a length of the chamber is less than or as long as four times a width of the entrance, optionally less than or as long as three times the width of the entrance. The length of the chamber is the dimension of the chamber from the entrance to an opposite end of the chamber. The length may be measured transversely to the entrance. The length may be measured along a rectilinear direction or along a curved direction, depending on the shape of the chamber. The width of theentrance may be measured transversely to the greatest dimension of the entrance.

[0015] Thanks to this ratio, the microstructure remains small enough to facilitate manipulation. This also ensures that the target is not enabled to move too much inside the chamber, as enabling large movements of the target inside the chamber might help it to accidentally find its way out.

[0016] Optionally, the microstructure is devoid of any articulated part. Therefore, the microstructure is easy to manufacture and reliable in use.

[0017] Optionally, the microstructure is rigid. Rigid means that the microstructure, besides not comprising any articulated part, does not deform under forces occurring during normal use thereof, including manipulation in the fluid medium, capturing and releasing the target, etc. A rigid microstructure is more resistant than a deformable structure.

[0018] Optionally, the chamber comprises a vent opposite the entrance. The vent may open out into the fluid medium. The vent facilitates movements of the microstructure in the fluid medium and renewal of the fluid medium within the chamber, which may be important e.g. to keep microorganisms alive.

[0019] Optionally, any path from the chamber to an outside of the chamber, other than the entrance, has at least one cross-section narrower than the entrance. The chamber may not necessarily have any other opening than the entrance. However, in case such another opening is provided, a path from the chamber to an outside of the chamber is defined through that opening. In these embodiments, said path has at least one cross-section narrower than the entrance, in order to ensure that the target that entered through the entrance cannot exit via the path. That is, in particular, the narrowest cross-section of the path may be smaller than the largest cross-section of the target.

[0020] Optionally, the microstructure comprises at least one prechamber connected in series to the entrance. Providing at least one prechamber, in addition to the chamber, may facilitate capturing the target into the chamber and / or impeding the target from exiting the chamber.

[0021] Optionally, the at least one pre-chamber comprises a plurality of pre-chambers communicating with one another.

[0022] Optionally, the microstructure is remotely controllable. For instance, the microstructure further comprises at least one handle for remote manipulation. The handle may be rigidly connected to the chamber. The handle may have features to enable remote manipulation such as magnetic manipulation (e.g. through a magnetic field), optic manipulation (e.g. through optical tweezers), acoustic manipulation and the like. A plurality of handles may be provided to enable orienting the microstructure, e.g. two, three, four or five handles. The handles may have any suitable shape, not necessarily resembling a mechanical handle. For instance, the handles may have a convex shape. In an embodiment, the handles may have the shape of e.g. a polyhedron, a sphere or an ellipsoid. For instance, spherical handles help stabilizing optical tweezers. The handles may be identical to one another or differ from one another.

[0023] Optionally, the microstructure further comprises at least one pillar to support the chamber, e.g. with respect to a floor or support surface. The pillar may extend beyond the chamber. The pillar may be thinner than the chamber. Thanks to the pillar, adhesion with the floor or support surface is reduced, and manipulation of the microstructure is therefore facilitated. In an example, the pillar may be thinner than the chamber. At least three pillars may be provided to enhance stability.

[0024] Depending on the embodiment, the pillars and the handles may be embodied by the same components of the microstructure, or as separate components.

[0025] Optionally, a material of the microstructure has a refractive index greater than a refractive index of the fluid medium. The material may be a material of the handles, as the case may be. Such a refractive index enables to manipulate the microstructure by optical tweezers. For instance, a material of the microstructure may have a refractive index greater than or equal to 1.3, e.g. if the surrounding medium is water-like. For instance, polymers such as photoresins may have a refractive index ranging from 1.4 to 1.7.

[0026] Optionally, the microstructure comprises a ferromagnetic material or a paramagnetic material. A ferromagnetic or paramagnetic material is influenced by an external magnetic field. Said material may be a material of the handles, as the case may be. Such a material enables to manipulate the microstructure by appropriate magnetic fields.

[0027] Optionally, the microstructure is asymmetric with respect to a longitudinal plane thereof. As defined below, a longitudinal plane is a plane of the microstructure passing through the entrance and an end of the chamber opposite the entrance. When the microstructure, e.g. the chamber, is asymmetric with respect to such a longitudinal plane, the target can be more reliably trapped in the chamber.

[0028] Optionally, the entrance is provided adjacent an inclined wall configured to lead the target into the chamber. Said wall may be inclined towards the inside of the chamber. Therefore, entry is facilitated and exit is made more difficult for the target.

[0029] Optionally, the entrance is provided in a concave wall of the chamber. From another point of view, the microstructure defines a convex cavity outside the chamber, adjacent the entrance. Therefore, entry is facilitated and exit is made more difficult for the target.

[0030] Optionally, the target is a microorganism or a cell, such as a spermatozoon, toxoplasma gondii or a microalga. Manipulation of microorganisms has many applications in various fields, and the proposedmicrostructure has proven to be particularly effective for manipulating microorganisms, including motile microorganisms or cells such as a spermatozoon, toxoplasma gondii or a microalga.

[0031] The present disclosure further relates to a method for capturing and manipulating a target, such as a motile target, in a fluid medium, comprising:- capturing the target in a chamber of a microstructure;- moving the microstructure enclosing the target;- releasing the target by moving the microstructure around the target so as to extract the target from the chamber.

[0032] The method may use the above-defined microstructure, which may have any of the features described herein.

[0033] The chamber enables the target to be manipulated reliably from one point to another. Besides, since the releasing is achieved by moving the microstructure around the target, no complex mechanism or articulated microstructure is required. Therefore, simplicity and reliability are improved.

[0034] Moving the microstructure around the target means that a relative movement between the microstructure and the target is obtained by controlling the microstructure to move as a whole while considering the target as a reference point.

[0035] Optionally, the chamber is as large as or narrower than three times a width of the target. Owing to this ratio, the chamber is not excessively large as compared to the target. This ensures that the target is not enabled to move too much inside the chamber, as enabling wide movements of the target inside the chamber might help it to find its way out accidentally. In addition or as an alternative, the chamber may be at least as long as the target, or at least as long as a part of the target that it is desired to accommodate in the chamber. For instance, in the aboveexample of flagellated cells or microorganisms, the length of the chamber may be greater than or equal to the length of the target's head.

[0036] Optionally, the releasing comprises moving the microstructure with respect to the target according to a relative movement substantially reversed as compared to a capturing movement. The capturing movement may be performed by the microstructure and / or by the target if the target is motile. Conversely, it is preferred that the microstructure is sized not to enable the target to exit the chamber on its own. Accordingly, to release the target, the microstructure is moved with respect to the target. The releasing movement may correspond to the reversed capturing trajectory, although the speed may vary. For instance, if the target is motile, the movement of the microstructure for releasing the target may be quicker than the target's own motion.

[0037] Optionally, the target comprises a gamete and the releasing is carried out in a medium comprising a complementary gamete. A complementary gamete is a gamete of the opposite sex to the target. In such embodiments, the proposed method enables to efficiently get gametes close to each other, e.g. for in vitro fertilization.BRIEF DESCRIPTION OF THE DRAWINGS

[0038] The invention and advantages thereof will be better understood upon reading the detailed description which follows, of embodiments given as non-limiting examples. This description refers to the appended drawings, wherein:- Fig. 1 is a perspective sectional view of a microstructure according to a first embodiment;- Fig. 2 is a cross-section of the microstructure of Fig. 1 along plane II-II;- Fig. 3 is a diagram illustrating a method for capturing and manipulating a target according to an embodiment;- Fig. 4 is a cross-section of a microstructure according to a second embodiment;- Fig. 5 is a cross-section of a microstructure according to a third embodiment;- Fig. 6 is a cross-section of a microstructure according to a fourth embodiment;- Fig. 7 is a perspective rear view of a microstructure according to a fifth embodiment- Fig. 8 is a top view of a microstructure according to a sixth embodiment.DETAILED DESCRIPTION OF EMBODIMENTS

[0039] A microstructure 10 according to a first embodiment is described with reference to Figs. 1 and 2. The microstructure 10 enables to capture and manipulate a target, as will be detailed hereinafter. Without loss of generality, it is assumed herein that the target is a motile spermatozoon. However, the target may be any motile or immobile object, e.g. a particle, a microorganism or a cell, for instance toxoplasma gondii or a microalga. For the sake of reference, a human spermatozoon's head measures about 5x3x1.5pm, and has a flagella extending over about 50- 70pm.

[0040] The microstructure 10 may be used in a fluid medium, e.g. a monophasic or multiphasic medium such as a liquid, a gas or a mixture thereof. In biological manipulations, the fluid medium is generally a liquid, however alternatives are also encompassed. The fluid medium may be a medium in which the target may be found and manipulated.

[0041] As mentioned above, the microstructure 10 comprises at least one chamber 12 provided with an entrance 14. The chamber 12 may be defined by a wall 16 and the entrance may be provided as an opening in the wall 16. The chamber 12 extends along an axial direction X which defines a front-rear direction, the entrance 14 being located at the rear ofthe chamber 12. Transverse directions Y (width) and Z (height) are defined so that (X, Y, Z) forms an orthogonal reference frame.

[0042] The wall 16 may be annular about the axial direction X. Here, the wall 16 is axisymmetric about the axial direction X, but other cross-sections than circles are contemplated, e.g. polygonal (e.g. rectangular), curved or a combination thereof. As best seen in Fig. 2, the cross-section of the wall 16 may be constant or varying. Specifically, the wall 16 may comprise a tubular portion 16a that is connected to a front end portion 16b and rear end portion 16c. The front end portion 16b may be planar or, as illustrated, convex towards to the outside of the chamber 12, e.g. conical. The rear end portion 16c may be planar, as illustrated, or non-planar, e.g. conical, as will be described later on. The entrance 14 may be provided in the rear end portion 16c. As shown in Figs. 1 and 2, the tubular portion 16a of the wall 16 may extend to the rear beyond the rear end portion 16c.

[0043] In this embodiment, the wall 16 is configured to retain its shape when submitted to external forces such as impact of the target inside or outside the chamber 12, movement within the fluid medium, etc. Besides, the microstructure 10 may be rigid, in particular devoid of any articulated part such as a releasing mechanism, a hinged door, movable arms or the like.

[0044] The entrance 14 may be centered, as illustrated, or transversely offset, with respect to the axial direction X. In this embodiment, the entrance 14 is circular, however other shapes are contemplated, e.g. polygonal, elliptic, curved, portions thereof and combinations of these.

[0045] As defined above and as apparent in Figs. 1 and 2, a crosssection of the entrance 14 is smaller than a cross-section of the chamber 12. In this case, both the entrance 14 and the chamber 12 have circular cross-sections perpendicular to the axial direction X, and a diameter dl4of the entrance 14 is less than a diameter dl2 of the chamber 12. For instance, a diameter dl2 of the chamber may range from 1pm to 20pm. However, in other cases, the height and / or the width of the entrance 14 may be less than the height and / or the width of the chamber 12. Thus, the rear end portion 16c having the entrance 14 forms a barrier limiting the target's ability to exit accidentally through the entrance 14. As best seen in Fig. 2, for instance, a spermatozoon 18 that has entered the chamber 12 may be brought to a side of the chamber 12 (e.g. in the Y or Z direction) and therefore prevented from exiting the chamber 12 even if the microstructure 10 is manipulated partly frontwards.

[0046] In order to limit movements of the sperm 18 inside the chamber 12 and prevent accidental exiting, the dimensions of the chamber 12 may be limited. For instance, a cross-section of the chamber 12 is less than or as large as three times (or even twice) the cross-section of the entrance 14. Thus, in the first embodiment, the following relationship may be complied with: dl4 < dl2 < 3 x dl4.

[0047] Of course, this relationship may be adapted, e.g. to width and / or height, when the entrance and / or the chamber are not circular.

[0048] Limitations of the chamber width may also be expressed in relation to the target: for instance, the chamber 12 may be as large as or narrower than three times a width dl8 of the target, e.g. of the sperm 18. That is: dl2 < 3 x dl8. Besides, for the target to get into the chamber 12, the entrance 14 is naturally wider than the target, e.g. here dl8 < dl4. Desirably, the entrance needs not be more than twice as large as the target, preferably 1.5 times as large.

[0049] Likewise but independently, the length 112 of the chamber 12 in the axial direction X may be limited, e.g. less than or as long as four times (or even three times) a width of the entrance. Thus, in the first embodiment, the following relationship may be complied with: Z12 < 4 x dl4. For instance, the length 112 of the chamber 12 may range from 1pmto 100pm. Besides, as mentioned above, the length 112 is preferably greater than or equal to the length of the microorganism or cell to accommodate, e.g. greater than or equal to the length of the target's head. In the example of a sperm 18 having a length of about 5pm, the length 112 of the chamber 12 may range from 5 pm to 30 pm, preferably from 7 pm to 15 pm.

[0050] The length or cross-section of the chamber 12 may not be constant, in which case the above features may apply to the greatest length and greatest cross-section, respectively.

[0051] As shown in Fig. 2, the chamber 12 may be sized to partially enclose the target: in this example, the chamber 12 is configured to accommodate the head of the sperm 18, however the flagella would at least partially remain outside the chamber 12.

[0052] Even if the sperm 18 is motile, it only swims frontwards. The relatively narrow dimensions of the chamber 12, and primarily the crosssection of the entrance 14 being smaller than the cross-section of the chamber 12, limits the risk that the sperm 18 accidentally exits the chamber 12 and is separated from the microstructure 10.

[0053] As shown in Figs. 1 and 2, the chamber 12 may comprise a vent 20 opposite the entrance 14. The vent 20 may be provided as an opening in the wall 16, specifically in the front end portion 16b. The vent 20 may be centered, as illustrated, or transversely offset, with respect to the axial direction X. In this embodiment, the vent 20 is circular, however other shapes are contemplated, e.g. polygonal, elliptic, curved, portions thereof and combinations of these.

[0054] The vent 20 is configured to allow fluid inside the chamber 12 and thus facilitate movement of the microstructure 10 in the fluidic medium. However, the sperm 18 should not be able to exit through the vent 20. In this respect, the following relationship may be complied with for the diameter d20 of the vent: d20 < dl8 < dl4. More generally, anyfluidic path from the chamber 12 to an outside of the chamber 12, other than the entrance 14, may have at least one cross-section narrower than the entrance 14 to ensure that the target cannot not exit the chamber 12 via that path. If a plurality of openings are provided in series along a path, at least one of these opening has a cross-section narrower than the entrance 14.

[0055] The microstructure 10 may comprise at least one handle 22 for remote manipulation. In the example depicted in Figs. 1 and 2, the microstructure 10 comprises two handles 22, however any number of handles is contemplated, e.g. three or more, four or more, etc. While a single handle 22 is enough for translating the microstructure 10, rotation can be achieved by controlling the relative positions of at least two handles 22, preferably at least three handles 22 for out-of-plane rotations, with respect to one another. Rotation is helpful in ensuring that the captured target does not exit the chamber 12 while the microstructure 10 is moving.

[0056] The handles 22 may be rigidly attached to the wall 16, so that movement of the handles 22 drives the microstructure 10 through the fluid medium. In the present embodiment, at least one pair of handles 22 are provided symmetrically on either side of the chamber 12.

[0057] The handles 22 may have any shape and size, and may comprise any material suitable for remote control by a remote controller.

[0058] For instance, the remote controller may be an optical remote controller, e.g. based on optical tweezers. In this respect, reference is made to the Applicant's international publications WO 2022 / 090760 Al and WO 2022 / 090761 Al. Respective optical tweezers may be used to control respective handles 22 of the microstructure 10.

[0059] To facilitate optical remote control, a material of the microstructure 10 may have a refractive index greater than a refractive index of the fluid medium, e.g. greater than 1.3, e.g. if the surroundingmedium is water. In practice, the material may have a refractive index of 1.4 or more, preferably 1.5 or more.

[0060] The aforementioned material may be a material of the handles 22. The parts of the microstructure 10 that need not be controlled remotely may have other features depending on their own requirements. Besides, part or all of the microstructure 10 (e.g. the wall 16, the handles 22, etc.) may be transparent to facilitate observation.

[0061] As illustrated in Figs. 1 and 2, the handles 22 may be spherical in order to optimize and stabilize the remote control through the optical tweezers. However, depending on the requirements of the chosen remote controller, the shape of the handles 22 may differ. The handles 22 may be connected to the wall 16 by arms 24, depending on the distance between the handles 22 and the wall 16. In embodiments, no arms 24 may be necessary, i.e. the handles 22 may be integral with the wall 16.

[0062] Instead of the optical remote controller, for instance, a magnetic remote controller may be used. To facilitate magnetic remote control, the microstructure 10, e.g. the handles 22, may comprise a ferromagnetic material or a paramagnetic material. Such a ferromagnetic or paramagnetic material may be plain or provided as fillers, as a coating, etc. of another material, that other material being e.g. a polymer.

[0063] Yet alternatively, in the case of an acoustic remote controller, the handles 22 may be controlled by acoustic tweezers. Acoustic tweezers rely on the acoustic contrast between the handles 22 and the surrounding medium, relating to acoustic-related properties such as density and compressibility.

[0064] Besides, the microstructure 10 may comprise at least one pillar 26 to support the chamber 12. In the example depicted in Figs. 1 and 2, the microstructure 10 comprises six pillars 26, however any number of handles is contemplated, e.g. two or more, three or more, four or more, etc. The pillars 26 may have any shape and size for supportingthe microstructure 10 with respect to a surface on which it rests. For instance, the pillars 26 may be provided as elongated members extending in the height direction Z. Each pillar 26 may extend towards both opposite sides of the microstructure 10, e.g. in the height direction Z. Besides, at least one pair of pillars 26 may be provided on either side of the chamber 12 in the width direction Y.

[0065] The pillars 26 may extend longitudinally beyond the wall 16 and / or the handles 22, desirably to form the single points of contact between the microstructure 10 and an underlying surface. Therefore, friction is reduced and movement of the microstructure is facilitated.

[0066] As shown in Figs. 1 and 2, front and rear pillars 26 may extend directly from the wall 16, whereas intermediate pillars 26 may extend from the handles 22. Of course, other configurations are contemplated.

[0067] Figure 3 illustrates a method for capturing and manipulating a target, such as a sperm 18, in a fluid medium, according to an embodiment. As defined above, the method comprises capturing the target (the sperm 18) in a chamber of a microstructure. In Fig. 3, the microstructure is depicted in a simplified manner. However, the abovedescribed microstructure 10 according to the first embodiment, or any other embodiment include those described below, may be used. Once the sperm 18 has been captured, the method comprises moving the microstructure 10 enclosing the sperm 18. For instance, the sperm 18 may thus be brought closer to an oocyte 28 (i.e. a complementary gamete to the sperm 18) in order to provoke fertilization. The microstructure 10 may be moved at least partially sideways and / or rearwards in order to avoid that the sperm 18 accidentally exits the chamber 12.

[0068] Once the sperm 18 has been brought to the desired location, the method comprises releasing the sperm 18 by moving the microstructure 10 around the sperm 18 so as to extract the sperm 18 fromthe chamber 12. Thus, there is no need for an articulated or otherwise complex system to release the sperm 18. In an example, the releasing comprises moving the microstructure 10 with respect to the sperm 18 according to a relative movement substantially reversed as compared to a capturing movement. That is, the microstructure 10 is moved as if the sperm 18 moved rearwards along the trajectory that the sperm 18 followed to enter the chamber 12.

[0069] Figures 4 to 8 illustrate the microstructure 10 according to other embodiments. In these figures, elements corresponding or identical to those of the first embodiment will be given the same reference sign and will not be described again.

[0070] The second embodiment of Fig. 4 differs from the first embodiment in that the entrance 14 is provided adjacent an inclined wall configured to lead the target into the chamber 12. Specifically, the rear end portion 16c may have a concave shape, e.g. a conical, half-elliptical or funnel-like shape, tapering towards the chamber 12. In this way, when the sperm 18 abuts against the rear end portion 16c outside the chamber 12, it is naturally guided towards the chamber 12. Conversely, accidentally exiting the chamber 12 is made more difficult.

[0071] The third embodiment of Fig. 5 is similar to that of Fig. 4, and differs in that the microstructure 10 further comprises at least one pre-chamber 30 connected in series to the entrance 14. The pre-chamber 30 may have a size similar or not to the chamber 12. In this embodiment, the pre-chamber 30 is defined by the tubular wall 16a which extends beyond the chamber 12, and is bounded on one side by the entrance 14 (or the rear end portion 16c), and on the other side by another opening 32 (e.g. formed in a pre-chamber rear wall 34).

[0072] When a plurality of pre-chambers 30 are provided, they may communicate with one another in series. The number of pre-chambers 30 may be adapted as desired.

[0073] It is noteworthy that in the third embodiment, the microstructure 10 comprises four handles 22 instead of two for the previous embodiments. This shows that the number of handles can be adapted as desired, e.g. based on the length of the microstructure 10. Besides, the pillars 26 may be provided adjacent the aforementioned arms 28, as will be best seen in Fig. 7, to that the handles 22 and the pillars 26 are independent components of the microstructure.

[0074] The fourth embodiment shown in Fig. 6 is similar to that of Fig. 5, but differs in that the pre-chamber rear wall 34 is convex instead of being concave. The pre-chamber 30 has an opening 32 opposite the entrance 14 and the pre-chamber rear wall 34 generally flares out from the opening 32 to the entrance 14. This facilitates controlled exit of the target from the pre-chamber 30, noting that the presence of a prechamber 30 per se makes accidental exit more difficult. For instance, the flared pre-chamber rear-wall may serve as a guide for the sperm flagella.

[0075] This embodiment illustrates that pre-chambers, wall designs and shapes, and opening sizes may be adapted as desired depending on the microstructure requirements and on the target to manipulate.

[0076] Figure 7 is a rear perspective view of the microstructure 10 according to a fifth embodiment, which differs from the microstructure 10 of the third embodiment (Fig. 5) by the shape of the rear end portion 16c of the wall 16, the pre-chamber rear wall 34 and, accordingly, the entrance 14 and the opening 32. In this embodiment, the rear end portion 16c extends inside the volume defined by the tubular wall 16a, from one side thereof towards the axial direction X, without reaching the opposite side of the tubular wall 16a. The hole left from the edge of the rear end portion 16c to said opposite side of the tubular wall 16a may form the entrance 14.

[0077] The rear end portion 16c may be planar. The rear end portion 16c may be inclined to lead the target into the chamber 12; forinstance, the free edge of the rear end portion 16c, which connects two points of the tubular wall 16a together, may be located more frontwards than the rest of the rear end portion 16c.

[0078] This embodiment is an example of the microstructure 10 being asymmetric with respect to a longitudinal plane thereof. However, other types of asymmetry are also contemplated.

[0079] The pre-chamber rear wall 34 may be shaped and sized similarly, even identically, to the rear end portion 16c. The pre-chamber rear wall 34 may be located opposite the rear end portion 16c, so that the pre-chamber rear wall 34 and the rear end portion 16c form a chicane for the target to get into the chamber 12. When the microstructure 10 comprises a chicane adjacent the chamber 12, the target can be more reliably secured.

[0080] Figure 8 is a top view of the microstructure 10 according to a sixth embodiment, which differs from the microstructure 10 of the fifth embodiment (Fig. 7) in that two pre-chambers 30 are provided. The microstructure 10, or at least the wall 16 of the chamber 12, may be made of transparent material so that the target (here a sperm 18) can be observed through the wall 16. As clearly shown in Fig. 8, the pre-chamber rear walls 34 and the rear end portion 16c are positioned on alternate sides of the microstructure 10 along the longitudinal direction X. The target must meander into the chamber 12, which enables to secure it more tightly. The pre-chamber(s) 30 may receive part of the sperm's flagella.

[0081] The microstructure 10 may be produced by additive or subtractive manufacturing, such a three-dimension laser writing, or two- photon polymerization. However, other manufacturing methods are contemplated, such as molding.

[0082] Although the present disclosure refers to specific exemplary embodiments, modifications may be provided to these examples withoutdeparting from the general scope of the invention as defined by the claims. In particular, individual characteristics of the different illustrated / mentioned embodiments may be combined in additional embodiments. Therefore, the description and the drawings should be considered in an illustrative rather than in a restrictive sense.

Claims

CLAIMS1. A microstructure (10) for capturing and manipulating a target (18), such as a motile target, in a fluid medium, the microstructure (10) comprising at least one chamber (12) provided with an entrance (14), wherein a cross-section of the entrance (14) is smaller than a crosssection of the chamber (12).

2. The microstructure of claim 1, wherein a cross-section of the chamber (12) is less than or as large as three times the cross-section of the entrance (14), optionally less than or as large as twice the crosssection of the entrance (14).

3. The microstructure of claim 1 or 2, wherein a length of the chamber (12) is less than or as long as four times a width of the entrance (14), optionally less than or as long as three times the width of the entrance (14).

4. The microstructure of any one of claims 1 to 3, wherein the microstructure (10) is devoid of any articulated part.

5. The microstructure of any one of claims 1 to 4, wherein the chamber (12) comprises a vent (20) opposite the entrance (14).

6. The microstructure of any one of claims 1 to 5, wherein any path from the chamber (12) to an outside of the chamber (12), other than the entrance (14), has at least one cross-section narrower than the entrance7. The microstructure of any one of claims 1 to 6, comprising at least one pre-chamber (30) connected in series to the entrance, optionally wherein the at least one pre-chamber (30) comprises a plurality of prechambers communicating with one another.

8. The microstructure of any one of claims 1 to 7, further comprising at least one handle (22) for remote manipulation.

9. The microstructure of any one of claims 1 to 8, further comprising at least one pillar (26) to support the chamber.

10. The microstructure of any one of claims 1 to 9, wherein a material of the microstructure (10) has a refractive index greater than a refractive index of the fluid medium, optionally wherein a material of the microstructure (10) has a refractive index greater than or equal to 1.3.

11. The microstructure of any one of claims 1 to 10, wherein the microstructure (10) comprises a ferromagnetic material or a paramagnetic material.

12. The microstructure of any one of claims 1 to 11, wherein the microstructure (10) is asymmetric with respect to a longitudinal plane thereof.

13. The microstructure of any one of claims 1 to 12, wherein the entrance (14) is provided adjacent an inclined wall (16c) configured to lead the target (18) into the chamber (12).

14. The microstructure of any one of claims 1 to 13, wherein the target (18) is a microorganism or a cell, such as a spermatozoon, toxoplasma gondii or a microalga.

15. A method for capturing and manipulating a target (18), such as a motile target, in a fluid medium, comprising:- capturing the target (18) in a chamber (12) of a microstructure (10);- moving the microstructure (10) enclosing the target (18);- releasing the target (18) by moving the microstructure (10) around the target (18) so as to extract the target from the chamber (12).

16. The method of claim 15, wherein the chamber (12) is as large as or narrower than three times a width of the target (18).

17. The method of claim 15 or 16, wherein the releasing comprises moving the microstructure (10) with respect to the target (18) according to a relative movement substantially reversed as compared to a capturing movement.

18. The method of any one of claims 15 to 17, wherein the target comprises a gamete (18) and the releasing is carried out in a medium comprising a complementary gamete (28).

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