METHODS AND APPARATUS FOR PROVIDING BIOLOGICAL SAMPLES IN A VITRIFIED STATE FOR STATIC AND TIME-RESOLVED STRUCTURAL INVESTIGATIONS USING ELECTRON OR X-RAY SOURCES

Abstract

The invention relates to a method for vitrifying a biological sample. The method includes positioning a sample holder with the biological sample by a transfer device in a starting position. The sample holder has a base and a pin projecting from the base along a holder axis. Further, the biological sample is attached to the pin distant from the base. The method further comprises adding a liquid to the biological sample in the starting position by a liquid dispenser. Further, the method comprises moving the sample holder with the biological sample by the transfer device along a predetermined transfer path from the starting position to a release position, wherein the biological sample in the release position is arranged in or adjacent to a liquefied gas. It is provided that the transfer path is inclined with respect to the holder axis or runs along a circular arc. Furthermore, the invention relates to a vitrification apparatus which is configured to perform the method.

Claims

1. A method for vitrifying a biological sample, comprising the steps: positioning a sample holder with the biological sample by a transfer device in a starting position, wherein the sample holder has a base and a pin projecting from the base along a holder axis, and wherein the biological sample is attached to the pin distant from the base; adding a liquid to the biological sample in the starting position by a liquid dispenser; moving the sample holder with the biological sample by the transfer device along a predetermined transfer path from the starting position to a release position, wherein the biological sample is located in or adjacent to a liquefied gas in the release position; wherein the transfer path is inclined with respect to the holder axis.

2. The method according to claim 1, wherein: the transfer path is straight or extends without a change of direction.

3. The method according to claim 1, wherein: the movement of the sample holder with the biological sample from the starting position to the release position comprises solely a translatory movement.

4. The method according to claim 1, wherein the transfer path is inclined with respect to the holder axis by an inclination angle, wherein the inclination angle: a) is an angle between 5° and 45°; or b) between 10° and 30°; or c) between 10° and 20°

5. The method according to claim 1, wherein the transfer path is inclined with respect to the holder axis by an inclination angle, wherein the inclination angle is greater than a threshold angle, β.sub.min, where the threshold angle is determined by β.sub.min=arctan((D/2−M+N)/L), where D is a lateral dimension of the base, M is a predetermined maximum distance between the liquid dispenser and the biological sample, N is a predetermined safety distance between the liquid dispenser and the base, and L is a length of the pin.

6. The method according to claim 1, wherein the holder axis is oriented along the direction of gravity in the starting position.

7. The method according to claim 1, wherein the transfer path extends in such a way that the sample holder and the transfer device move past the liquid dispenser without collision when moving from the starting position to the release position.

8. The method according to claim 1, wherein between adding the liquid in the starting position and moving the sample holder with the biological sample from the starting position to the release position a predetermined period of time is waited or a position of the liquid dispenser is not altered.

9. The method according to claim 1, further comprising: optically exciting the biological sample in the starting position with at least one light pulse by an irradiation device.

10. The method according to claim 1, further comprising: providing a predetermined humidity or temperature in an environment of the sample in the starting position by a conditioning device.

11. The method according to claim 1, further comprising: releasing the sample holder with the biological sample from the transfer device in the release position by a release device of the transfer device, so that the sample holder can fall off the transfer device by gravity.

12. A method for vitrifying a biological sample, comprising the steps: positioning a sample holder with the biological sample by a transfer device in a starting position, wherein the sample holder has a base and a pin projecting from the base along a holder axis, and wherein the biological sample is attached to the pin distant from the base; adding a liquid to the biological sample in the starting position by a liquid dispenser; moving the sample holder with the biological sample by the transfer device along a predetermined transfer path from the starting position to a release position, wherein the biological sample is located in or adjacent to a liquefied gas in the release position; wherein the transfer path runs along a circular arc.

13. The method of claim 10, wherein: the transfer path runs substantially along a quarter circular arc.

14. The method of claim 10, wherein: the movement of the sample holder with the biological sample from the starting position to the release position comprises solely a rotational movement.

15. The method of claim 10, wherein the holder axis is oriented substantially perpendicular to the direction of gravity in the starting position.

16. The method of claim 10, wherein the method further comprises the features of one of claims 7 to 11.

17. A vitrification apparatus configured to perform a method according to one of the preceding claims, comprising: a container for receiving the liquefied gas; a transfer device with a mount for holding the sample holder with the biological sample, wherein the transfer device is configured to position the sample holder with the biological sample mounted in the mount in the starting position and to move it along the predetermined transfer path from the starting position to the release position; and a liquid dispenser for adding the liquid to the biological sample in the starting position.

18. The vitrification apparatus according to claim 17, further comprising: an irradiation device arranged to optically excite the biological sample in the starting position by at least one light pulse.

19. The vitrification apparatus according to claim 17, further comprising: a conditioning device configured to provide a predetermined humidity or temperature in an environment of the biological sample in the starting position.

20. The vitrification apparatus according to claim 17, further comprising: a release device by which the sample holder with the biological sample can be released from the transfer device or from the mount for a removal of the sample holder.

21. The vitrification apparatus according to claim 17, further comprising: a storage device which is arranged in the container and which has at least one receptacle in which the sample holder with the biological sample can be accommodated, wherein the storage device preferably being arranged in such a way that, when the sample holder with the biological sample is in the release position, the at least one receptacle is arranged below the sample holder with the biological sample.

Description

FIGURE DESCRIPTION

[0052] FIG. 1: A flow diagram of a method for vitrifying of a biological sample according to one embodiment;

[0053] FIG. 2: A schematic representation of a vitrification apparatus according to one embodiment, wherein the sample holder with the biological sample is in the starting position;

[0054] FIG. 3: A schematic representation of the vitrification apparatus shown in FIG. 2, with the sample holder containing the biological sample in the release position;

[0055] FIG. 4: A further schematic representation of the vitrification apparatus shown in FIGS. 2 and 3;

[0056] FIG. 5: A schematic representation of the geometric relationships between the sample holder and the liquid dispenser for determining a threshold angle for an inclination angle of the transfer path according to one embodiment; and

[0057] FIG. 6: A schematic representation of a vitrification apparatus according to a further embodiment, wherein the sample holder with the biological sample is in the starting position.

[0058] Identical or functionally equivalent elements are described in all figures with the same reference signs and in some cases are not described separately.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

[0059] FIG. 1 shows a flow chart of a method for vitrifying a biological sample 1. The biological sample 1 may be, for example, an organic substance such as biomolecules. In step S.sub.1, a sample holder 2 with the biological sample 1 is positioned by a transfer device 12 in a first position P.sub.1, referred to as starting position. In other words, preferably, the sample holder 2 with the biological sample 1 is brought into a predetermined position (=starting position N). The starting position N may thereby preferably refer to a location and/or an orientation of the sample holder 2 with the biological sample 1 in three-dimensional space. The sample holder 2 should preferably have a base 2a and a pin 2b projecting from the base 2a along a holder axis A. For example, the sample holder 2 may be a sample holder 2 according to the SPINE-standard. Preferably, it is provided that the biological sample 1 is attached to the pin 2b (e.g., by a mesh or microscopic loop) distant from the base 2a. For example, a distance between the biological sample 1 and a bottom of the base 2a oriented opposite to the pin 2b may be 22 mm.

[0060] In step S.sub.2, a liquid (e.g. water or a liquid solution of an active substance) is added to the biological sample 1 in the starting position N by a liquid dispenser 13. Preferably, adding the liquid serves to start a, e.g. chemical and/or enzymatic reaction in the biological sample 1. The liquid dispenser 13 may be configured to add the liquid to the biological sample 1 dropwise, e.g. with an average droplet size of about 50 μm and/or a droplet generation rate of about 1-2 kHz. The liquid dispenser 13 may further be spaced a few millimeters, preferably <1 mm, from the biological sample 1 to add the liquid. Accordingly, the method may further comprise positioning the liquid dispenser 13 such that the liquid dispenser 13, in particular a liquid outlet of the liquid dispenser 13, is spaced from the biological sample 1 in the starting position P.sub.1 less than 2 mm, preferably less than 1 mm.

[0061] In step S.sub.3, the sample holder 2 with the biological sample 1 is moved by the transfer device 12 along a predetermined transfer path T from the first position or starting position P.sub.1 to a second position P.sub.2, referred to as release position. The movement of the sample holder 2 with the biological sample 1 may also be referred to as transferring. The term transfer path T may preferably denote the path of movement of the sample holder 2 with the biological sample 1 from the starting position P.sub.1 to the release position P.sub.2. For example, the transfer path T may be the path of movement of the center of gravity of the sample holder 2 and/or the sample 1. Here, it is envisaged that the biological sample 1 is located in or adjacent to a liquefied gas 3 in the release position P.sub.2. Liquefied gas 3, which may also be referred to as liquid gas, is preferably to be understood as a gas 3 liquefied by cooling and/or compression, which remains cold and liquid at normal pressure due to the enthalpy of vaporization. For example, the liquefied gas 3 may be liquid nitrogen, liquid methane and/or liquid ethane. Depending on whether the release position P.sub.2 is located in the liquefied gas 3 or adjacent thereto, vitrifying of the biological sample 1 may take place in the release position P.sub.2 either immediately or after a corresponding immersion of the biological sample 1 in the liquefied gas 3 (e.g., after releasing the sample holder 2 from the transfer device 12 and a subsequently free falling into the liquefied gas 3). Advantageously, the current state of the biological sample 1 (e.g., a reaction intermediate produced by the liquid addition) may thus be preserved for subsequent investigations (e.g., at a synchrotron radiation source).

[0062] The corresponding method is characterized by the fact that the aforementioned transfer path T is inclined with respect to the holder axis A (alternative 1) or that the transfer path T runs along a circular arc (alternative 2), which will be described in more detail in connection with FIGS. 3 and 6.

[0063] Furthermore, a preferred embodiment provides that the above-described procedure is carried out for several biological samples 1 (e.g., in parallel or successively), with the respective procedures differ in a respective time delay between the adding of the liquid and the start of the movement of the sample holder 2 with the biological sample 1. By way of example only, ten biological samples 1 may thus be vitrified with ten different (e.g. increasing) time delays, in order to be able to gain knowledge in an advantageous manner about the temporal behavior of the reaction or the temporal change in the structure of the biological samples 1 by subsequent structural investigations of the biological samples 1 at a synchrotron radiation source.

[0064] FIGS. 2 to 4 show various schematic illustrations of a vitrification appa-ratus 10 according to one embodiment. The vitrification apparatus 10 is configured to perform one of the methods described in this document (e.g. in connection with FIG. 1).

[0065] For this purpose, the vitrification apparatus 10 may comprise a container 11 for receiving the liquefied gas 3. For example, the container 11 may be configured to receive liquid nitrogen and/or liquid methane. For example, the container 11 may be tub-shaped. The container 11 may be fillable with the liquefied gas 3 up to a given target fill level. The container 11 may have a lid 11a with at least one recess 11b (for example, a cut-out). The lid 11a with the with at least one recess 11b may close the container 11 from above, whereby access from the outside into the interior of the container 11 should preferably be possible via the at least one recess 11b. Preferably, the at least one recess 11b is configured to allow for inserting of the sample holder 2 or biological sample 1 into the interior of the container 11. The lid 11a may serve to thermally insulate the liquefied gas 3 received in the container 11 from the environment. That is, the lid 11a may reduce direct contact between the liquefied gas 3 and the ambient air. Further, the vitrification apparatus 10 may comprise a pump 20 (e.g., a diaphragm pump). The pump 20 may be used to draw (cold) gases generated above the liquefied gas 3, thereby reducing a generation of fog from residual moisture in the ambient air. For this purpose, the pump 20 may be in fluid communication, e.g. via a line connection 21 penetrating the lid 11a, with a region of the container 11 located between the lid 11a and the liquefied gas 3 or the target level.

[0066] The vitrification apparatus 10 may further comprise a transfer device 12 with a mount 12a for receiving the sample holder 2 with the biological sample 1. The mount 12a may, for example, be configured to secure the sample holder 2 with the biological sample 1 to the transfer device 12 in a form-fitting and/or force-fitting manner. For example, the mount 12a may comprise an electromagnet and/or a clamping device for this purpose. At least in sections, the mount 12a may be form-fitted to the sample holder 2. For example, an inner contour of the mount 12a may be formed at least in sections to match the shape of an outer contour of the base 2a of the sample holder 2. Furthermore, the transfer device 12 may comprise a release device 12b. The release device 12b may be configured to release a positive and/or non-positive connection between the sample holder 2 with the biological sample 1 and the transfer device 12. Via the release device 12b, the sample holder 2 with the biological sample 1 may thus be released from the transfer device 12 or the mount 12a for removal of the sample holder 2 with the biological sample 1.

[0067] The transfer device 12 may also be configured to position the sample holder 2 with the biological sample 1 received in the mount 12a, preferably a sample holder 2 configured according to the SPINE standard, in the starting position P.sub.1 (cf. FIG. 2). In other words, the transfer device 12 may be configured to hold the sample holder 2 with the biological sample 1 at a predetermined location and/or in a predetermined orientation in three-dimensional space by the mount 12a. Preferably, the starting position P.sub.1 is located above the container 11. Further, preferably, the holder axis A in the starting position P.sub.1 is oriented along the direction of gravity S. However, the holder axis A may also be oriented obliquely to the direction of gravity S. By way of example only, the mount 12a may have a downward oriented contact surface against which the base 2a of the sample holder 2 rests in the mounted state, so that the biological sample 1, which is attached to the pin 2b, is arranged below the base 2a in the starting position P.sub.1.

[0068] Further, the vitrification apparatus 10 may comprise at least one liquid dispenser 13 for adding the liquid to the biological sample 1 in the starting position N. The at least one liquid dispenser 13 may be configured to dispense the corresponding liquid dropwise (e.g., with droplet sizes of about 50 μm). The at least one liquid dispenser 13 may be configured to dispense a droplet sequence at a generation rate of 1-2 kHz, thereby advantageously generating a liquid film on the biological sample 1 in as controlled a manner as possible. For example, the at least one liquid dispenser 13 may here comprise a cannula fluidically connected to a liquid reservoir (not shown) and having an outlet opening. The outlet opening may be or may be positioned at a distance of a few millimeters, preferably at a distance <1 mm, from the biological sample 1. For this purpose, the vitrification apparatus 10 may comprise at least one adjustment device 14 (e.g., a linear adjuster) by which the at least one liquid dispenser 13 is movable. For example, the at least one liquid dispenser 13 and/or the outlet opening may be movable towards the biological sample 1 and/or retractable from the biological sample 1 by the at least one adjustment device 14. In a preferred embodiment, the at least one adjustment device 14 comprises at least two adjustment devices 14 (not separately referenced) for this purpose. For example, the at least two adjustment devices 14 may comprise a coarse adjustment device, by which the at least one liquid dispenser 13 may be moved over greater distances (e.g., in order to obtain better access for changing the sample holder 2), and a fine adjustment device, by which it is possible to position the at least one liquid dispenser 13 or the outlet opening on the biological sample 1 as precisely as possible. By supplying the liquid or wetting the biological sample 1 by the at least one liquid dispenser 13, a chemical and/or enzymatic reaction may be triggered in the biological sample 1, for example.

[0069] In order to position the at least one liquid dispenser 13 as precisely as possible on the biological sample 1, the vitrification apparatus 10 may further comprise at least one macro camera 19. Preferably, the at least one macro camera 19 comprises multiple (e.g., two) macro cameras 19, which are preferably aligned to the biological sample 1 at different viewing angles. The at least one macro camera 19 may be arranged to capture a spatial area around the biological sample 1 in the starting position P.sub.1. Preferably, one of the at least one macro camera 19 is thereby arranged oriented perpendicular to a direction of movement of the at least one liquid dispenser 13. The vitrification apparatus 10 may further comprise an output device (e.g., a display screen) (not shown) on which image data captured by the at least one macro camera 19 is displayed.

[0070] Furthermore, the vitrification apparatus 10 may comprise a, preferably switchable, irradiation device 15. The irradiation device 15 (e.g., a laser) may be arranged to optically excite the biological sample 1 in the starting position P.sub.1 by at least one light pulse. In other words, by the irradiation device 15, the biological sample 1 may be irradiated with a light pulse generated by an irradiation device 15. Accordingly, in the starting position P.sub.1, the biological sample 1 may preferably be located in the optical path of the irradiation device 15 (indicated by the dashed line). In addition or alternatively to moistening the biological sample 1 in the starting position P.sub.1, a reaction may thus also be induced and/or influenced in the biological sample 1 in an advantageous manner.

[0071] The vitrification apparatus 10 may further comprise a conditioning device 16. The conditioning device 16 may be configured to provide a predetermined humidity and/or temperature in an environment of the biological sample 1 in the starting position N. For example, the conditioning device 16 may be configured to generate a water mist and/or temperature-controlled air in the environment of the biological sample 1 in the starting position N. In other words, by the conditioning device 16, a controlled atmosphere may be provided in the vicinity of the biological sample 1. In an advantageous manner, the biological sample 1 may thereby be protected from drying out. In addition or alternatively, constant reaction conditions may also be provided in this way.

[0072] After appropriate preparation or modification of the biological sample 1 in the starting position P.sub.1, it may then be preserved or vitrified for subsequent investigations (e.g. at a synchrotron radiation source). For this purpose, the transfer device 12 may be configured to move the sample holder 2 with the biological sample 1 accommodated in the mount 12a along the predetermined transfer path T from the starting position P.sub.1 to the release position P.sub.2 (cf. FIG. 2). That is, the transfer device 12 may be configured to transfer the sample holder 2 with the biological sample 1 along the predetermined transfer path T from the starting position Pito the release position P.sub.2 by the mount 12a. In the release position P.sub.2, the biological sample 1 may be arranged in the liquefied gas 3 (e.g. liquid nitrogen or liquid ethane)—as shown. Accordingly, in the release position P.sub.2, vitrification or shock freezing of the biological sample 1 may occur immediately. In an alternative variant, the biological sample 1 may also initially still be arranged above the liquefied gas 3 or above the target fill level in the release position P.sub.2 (not shown). Preferably, in the release position P.sub.2, the biological sample 1 is arranged adjacent to the liquefied gas 3 or the target level. In other words, in the release position P.sub.2, the biological sample 1 may be located in the immediate vicinity of the liquefied gas 3 or the target level, e.g., less than 1 cm away from the liquefied gas 3 or the target level. In this embodiment, vitrification of the biological sample 1 may take place after a release of the sample holder 2 with the biological sample 1 from the transfer device 12 or the mount 12a by the release device 12b and a subsequent gravity-mediated falling of the sample holder 2 with the biological sample 1 into the liquefied gas 3.

[0073] Preferably, the vitrification apparatus 10 comprises a storage device 17. The storage device 17 may be arranged in the container 11 for receiving the liquefied gas 3. The storage device 17 may, for example, be in the form of a rotatable magazine. The storage device 17 may have at least one receptacle 17a. Preferably, the at least one receptacle 17a has a plurality (for example, ten) of receptacles 17a. The biological sample 1 may be receivable in the at least one receptacle 17a. Preferably, the at least one receptacle 17a is thereby configured such that the biological sample 1 received in the at least one receptacle 17a is not in direct contact with the storage device 17. For example, the at least one receptacle 17a may be in the form of a cylindrical and/or vial-shaped container. Preferably, a diameter of the container is adapted to a diameter of the base 2a of the sample holder 2 in such a way that the base 2a may be accommodated in the container only partially. Further preferably, the at least one receptacle 17a together with the sample holder 2 with the biological sample 1 may be removed on the storage device 17. Furthermore, the storage device 17 may be arranged in such a way that, when the sample holder 2 with the biological sample 1 is in the release position P.sub.2, the at least one receptacle 17a is arranged directly below the sample holder 2 with the biological sample 1. In an advantageous manner, the sample holder 2 with the biological sample 1 may thereby fall into the at least one receptacle 17a of the storage device 17 in a gravity-mediated manner and thus quasi-automatically after being released from the mount 12a of the transfer device 12 by the release device 12b. In a further variant, it may also be provided that the vitrification apparatus 10 only has a corresponding attachment point for attaching the storage device 17, without the storage device 17 itself being a mandatory component of the vitrification apparatus 10.

[0074] After the configuration of the vitrification apparatus 10 in the starting position P.sub.1 (FIG. 2) and in the release position P.sub.2 (FIG. 3) have been discussed above, the transfer path T and the transfer movement will be discussed again below with reference to FIG. 4. In this embodiment, it is provided that the transfer path T is inclined with respect to the holder axis A. As mentioned above, the term transfer path T shall preferably refer to the path of movement of the sample holder 2 with the biological sample 1 from the starting position P.sub.1 to the release position P.sub.2. For example, the transfer path T may be the path of movement of the center of gravity of the sample 1 (cf. dashed line in FIG. 4). As shown by way of example, the transfer path T may be inclined at an inclination angle β of 45° with respect to the holder axis A. Preferably, however, an angle of inclination β of between 10° and 20° is provided. Furthermore, the transfer path T in this embodiment preferably extends without a change of direction. Accordingly, the movement of the sample holder 2 with the biological sample 1 from the starting position P.sub.1 to the release position P.sub.2 may comprise here, by way of example, exclusively a translational movement. It is further preferred that a duration of the transfer movement is in the range of a few tenths to a hundred milliseconds (e.g. 50 ms).

[0075] For this purpose, the transfer device 12 may, for example, have (e.g., pneumatic and/or hydraulic) actuators and/or guides to enable appropriate movement of the sample holder 2 with the biological sample 1. For example, in the present embodiment, the transfer device 12 may have a (e.g., pneumatic) linear unit configured to move the mount 12a or the sample holder 2 with the biological sample 1 along a straight line. In this context, it should be noted that the sample holder 2 with the biological sample 1 is not necessarily a component of the vitrification apparatus 10, but the vitrification apparatus 10 is merely configured to enable a corresponding movement of the corresponding components along the transfer path T. In one variant, however, the vitrification apparatus 10 may also comprise the sample holder 2 with the biological sample 1.

[0076] Preferably, it is further provided that by the vitrification apparatus 10 a time delay between the supply of the liquid in the starting position P.sub.1 and the movement of the sample holder 2 with the biological sample 1 from the starting position P.sub.1 to the release position P.sub.2 is adjustable. Via the aforementioned time delay, the state in which the biological sample 1 is ultimately vitrified after starting a reaction (by adding liquid) may be altered in an advantageous manner. This is particularly advantageous if the procedure is carried out for several (identical) biological samples 1 with different (e.g. increasing) time delays, in order to thereby investigate the temporal behavior of the reaction or the temporal change in the structure of the biological samples 1. To control the time delay, the vitrification apparatus 10 may comprise a control device 18. The control device 18 may be configured to operate the transfer device 12 and/or the at least one liquid dispenser 13 (e.g., with an adjustable time delay). By the control device 18, it may preferably be possible to control a time of the supply of the liquid by the at least one liquid dispenser 13 and/or a time of the start of the movement from the starting position P.sub.1 to the release position P.sub.2. Furthermore, the control device 18 may also be configured to operate the release device 12b, the irradiation device 15, the conditioning device 16 and/or the macro camera 19. In a preferred embodiment, the control device 18 further also comprises a safety device 18a, which is configured to block the transfer device 12 from extending during a change of the sample holder 2.

[0077] FIG. 5 shows a schematic representation of the geometric relationships between the sample holder 2 and a liquid dispenser 12 for defining a threshold angle β.sub.min for an inclination angle β of the transfer path T. As mentioned above, in one embodiment the transfer path T may run oblique to the holder axis A of the sample holder 2. In this regard, in order to advantageously avoid collisions with the liquid dispenser 12 when transferring the sample holder 2 with the biological sample 1, the transfer path T may run in-clined with respect to the holder axis A by an inclination angle β that is larger than a threshold angle β.sub.min. That is, the inclination angle β shall preferably have at least a value of β.sub.min here. This threshold angle β.sub.min may be given here by the relation β.sub.min=arctan((D/2−M+N)/L). Here, D denotes a lateral dimension of the base 2a. For example, D may be a diameter of the base 2a. The lateral dimension shall preferably denote a dimension of the pedestal 2a in a direction perpendicular to the holder axis A. M denotes a predetermined maximum distance between the liquid dispenser 13 and the biological sample 1. For example, M may have a value of 1 mm. The predetermined maximum distance between the liquid dispenser 13 and the biological sample 1 may be given by the perfor-mance or aiming accuracy of the liquid dispenser 13. N denotes a predetermined safety distance between the liquid dispenser 13 and the base 2a. For example, this may be used to account for possible inaccuracies in positioning. L designates a length of the pin 2b. Preferably, the length of the pin is the distance between the free (second) pin end and the base 2a.

[0078] FIG. 6 shows a schematic representation of a vitrification apparatus 10 according to a further embodiment. FIG. 6 serves primarily to illustrate the alternative transfer mechanism, which is why a number of the further optional components, e.g. the irradiation device 15, the conditioning device 16, etc., have been omitted. In contrast to the embodiment described above in connection with FIGS. 2 to 5, it is provided here that the transfer path T runs along a circular arc (cf. dashed line in FIG. 6). As shown by way of example, the transfer path T may thereby run essentially along a quarter circular arc. In other words, the holder axis A in the release position P.sub.2 may be oriented rotated by 90° to the holder axis A in the starting position P.sub.1. Preferably, the holder axis A is ori-ented perpendicular to the direction of gravity S in the starting position P.sub.1. However, the holder axis A may also be oriented obliquely to the direction of gravity S. Furthermore, moving the sample holder 2 with the biological sample 1 from the starting position P.sub.1 to the release position P.sub.2 may comprise only a rotational movement. For this purpose, the transfer device 12 may, for example, have corresponding actuators to enable a corresponding movement of the sample holder 2 with the biological sample 1. For example, in the present embodiment, the transfer device 12 may comprise a servomotor (not shown), wherein the mount 12a may be motion-coupled to the rotor of the servomotor, for example via a corresponding extension.

[0079] Although the invention has been described with reference to specific embodiments, it is apparent to the skilled person that various modifications may be made and equivalents may be used as substitutes without departing from the scope of the invention. Consequently, the invention is not intended to be limited to the disclosed embodiments, but is intended to encompass all embodiments that fall within the scope of the appended claims. In particular, the invention also claims protection for the subject matter and features of the dependent claims independent of the claims referenced therein.