WO2021122953A1

WO2021122953A1 - System for investigation of a small animal

Info

Publication number: WO2021122953A1
Application number: PCT/EP2020/086714
Authority: WO
Inventors: Timofey ROZHDESTVENSKIY; Boris SKRYABIN; Leonid GUBAR; Helena KAISER
Original assignee: Westfälische Wilhelms-Universität Münster
Priority date: 2019-12-17
Filing date: 2020-12-17
Publication date: 2021-06-24

Abstract

System (1) comprising a stand device (2), in particular a gynecological stand device, and a fixation device (3) configured to receive and hold an object, in particular an animal, to be investigated in position, wherein the stand device (3) comprises a housing (4) provided with a lightning device (7), and wherein the fixation device (3) is releasable attached to the stand device (2) in a position in which light of the lightning device illuminates an area of the object to be investigated received in the fixation device (3), in particular a genital tract of an animal.

Description

SYSTEM FOR INVESTIGATION OF A SMALL ANIMAL

The invention relates to a system for investigation of an object, in particular a small animal, wherein the system is suitable in particular for non-surgical embryo transfer procedure in mammals, particularly animals such as for example rodents, e.g., mice, rats or guinea pigs etc. and other relatively small size animals.

In US 2009/0292162 A1 a device having a catheter and a hub is disclosed for transfer of an embryo containing solution into the uterus of a mammal, for example, a small mammal such as a rat or mouse. The catheter's shape and tip is designed to simplify insertion and minimize injury to the mammal. The hub is designed to further control the insertion of the catheter and to interface with a pipette, for example, that provides the force required for the transfer of an embryo containing solution. As a result, the transfer can occur without requiring surgery.

However, said device used for non-surgical procedures results in low efficiency. In particular, said device does not permit the direct visual control of transferred embryos. In particular, the animals are not immobilized. The person performing an embryo transfer has to hold the animal in one hand and perform transfer with the other using the catheter and hub. During this procedure the animal can turn or move and if the catheters tip is introduced into vagina an animal will experience pain. Moreover this will lead to the additional loss of embryos. Therefore surgical embryo transfer remains the most popular procedure.

It is therefore an object of the invention to provide an improved system which allows investigation of an object, in particular an animal, e.g. a rodent, such as a mouse, rat or guinea pig etc. and which is in particular useful for non- surgical embryo transfer to or from said animal.

At least one of the above objects is achieved in accordance with the invention by providing a system comprising a stand device, in particular a gynecological stand device, and a fixation device configured to receive and hold an object, in particular an animal, to be investigated in position, wherein the stand device comprises a housing provided with a lightning device, and wherein the fixation device is releasable attached to the stand device in a position in which light of the lightning device illuminates an area of the object to be investigated received in the fixation device, in particular a genital tract of an animal.

The system has the advantage that an object in particular a small animal can be securely held in a defined position without requiring to hold the object, i.e., animal, with the hands. Furthermore, the area to be investigated can be illuminated by the lightning device of the system which significantly enhance investigation of the object.

According to an embodiment of the invention the stand device comprises an opening at a front wall of the housing in which the lightning device is directly received or wherein the lightning device is movably arranged within the housing in a direction toward and away from the opening, wherein the lightning device comprises preferably at least one lightning element and wherein the lightning element is in particular an LED or an LED-array. Moving the lightning element toward and away from the opening allows to provide to adapt the visualization. Moreover, LEDs as lightning element are space and energy saving.

In a further embodiment of the invention the lightning device is rotatably arranged within the housing.

In another embodiment of the invention the stand device comprises at least one optical element, preferably a lens and/or mirror. Thus the light beam of the lightning element can be controlled, e.g. scattered or focused dependent on the intended use. In general, the illumination of, e.g., mouse genital track is happening by directing for example an LED element (touching) to mouse abdominal area. Importantly, the LED light is preferably adjusted to directly touching mouse fur. While opening vagina with a gynaecological mirror (vaginal speculum) as described below, e.g., with respect to Fig. 7, operator can clearly observe under binocular microscope the vaginal area and entrances into uterus horns. Optionally one or more additional optical element(s) can also be applied to adjust the light beam.

According to an embodiment of the invention the stand device comprises an actuation device which is connected with the lightning device to move the lightning device at least in the direction toward and away from the opening in the front wall of the housing and/or to rotate the lightning device, wherein the actuation device preferably comprises a shaft which is connected to the lightning device and movably received within at least one guide slot provided in a corresponding side wall of the housing, wherein the shaft is movably arranged along the guide slot together with the lightning device toward and away from the opening in the front wall of the housing and/or rotatable around its longitudinal axis. The actuation device comprising a shaft, which is movably guided in at least one corresponding guide slot of the housing is simple to realize, space saving and cheap. In an embodiment of the invention the stand device comprises a receiving and holding unit for receiving and holding the fixation device in the position in which light of the lightning device illuminates an area of the object to be investigated and received in the fixation device, in particular a genital tract of an animal received in the fixation device. The receiving and holding unit allows a defined positioning of the fixation device at the stand and prevents an unintentional movement of the fixation device during investigation of the object.

In a further embodiment the fixation device comprises a tubular housing to receive the object to be investigated, wherein the tubular preferably comprises at least one head fixation unit, at least one hip fixation unit and/or at least one tail fixation element. Thus an object in particular an animal can be fixedly held in position within the tubular housing during investigation.

In an embodiment of the invention the at least one head fixation unit comprises a head receiving element, in particular a lid, and at least one actuation element to fix the head receiving element in position within the tubular housing, wherein the actuation element is configured to be movable in contact with the head receiving element to hold and fix the head receiving element in position and further movable out of contact with the head receiving element to release the head receiving element, wherein the actuating element preferably comprises a pin, wherein the pin comprises a thread section and wherein the tubular housing comprises a corresponding thread hole in which the pin with its thread section is received, wherein the pin with its thread section is screwed into the thread hole until the actuation element is in contact with the head receiving element to hold and fix the head receiving element in position. The actuation element comprising the pin and the thread section can be easily realized at low costs and further requires only little space.

According to a further embodiment of the invention the at least one hip fixation unit comprises at least one hip receiving element and at least one actuation element to fix the hip receiving element in position within the tubular housing, wherein the actuation element is releasably or fixedly connected to the hip receiving element and is configured to be movable together with the hip receiving element in contact with the hip region of an animal as object to be investigated to hold and fix the hip region of the animal in position and is further movable out of contact with the hip region of the animal to release the animal, wherein the actuation element preferably comprises a pin, wherein the pin comprises a thread section and wherein the tubular housing comprises a corresponding thread hole in which the pin with its thread section is received, wherein the pin with its thread section is screwed into the thread hole until the hip receiving element is in contact with the hip region of the animal to hold and fix the hip region of the animal in position. The hip receiving element allows a stable contact with the animal, so that the animal cannot move unintentionally within the tubular housing. Further the actuation element and the hip receiving element can be easily realized at low costs.

In an embodiment of the invention the tubular housing comprises a slot along its length, preferably along its entire length, and wherein the at least one tail fixation element is configured to be insertable in the slot and held in position when inserted in the slot. Such configuration allows a very simple positioning and fixation of an animal tail, so that the animal tail cannot move unintentionally during investigation.

In a further embodiment of the invention the fixation device comprises at least one holding means to hold a paw of an animal as object to be investigated, wherein the holding means is a slot formed at an end, in particular an upper end, of the tubular housing to receive the paw of the animal, wherein preferably on each side of the slot the tubular housing is provided with an additional protruding portion which is configured to attach a closing means, in particular an elastic ring or cover, to close and lock the open end of the slot. Such holding means can be also easily realized at low costs and further prevents in a simple manner an unintentional movement of the paws of the animal to be investigated.

In another embodiment the tubular housing comprises at its end, in particular the upper end, an opening which is large enough to allow investigation of a part of the object to be investigated, in particular a part of an animal to be investigated, preferably the genital tract of the animal, and wherein the opening of the tubular housing is preferably positioned adjacent or in front of the opening of the housing, when the tubular housing is attached to the stand device, wherein the tubular housing is preferably L-shaped or C-shaped, wherein the upper end of the housing is in particular positioned in an upright position when attached to the stand device in the position in which light of the lightning device illuminates an area of the object to be investigated received in the fixation device, in particular a genital tract of an animal. Thus, an animal can be positioned within the housing in an optimal position for investigation.

According to the invention a capillary tube system is provided, wherein the capillary tube system comprises a transparent capillary tube and a transparent adapter, wherein the transparent adapter is releasably connectable with an end of the transparent capillary tube and wherein the transparent adapter is preferably flexible and/or elastic. The transparent capillary tube and its transparent adapter allow direct visual control, which is in particular important when using said capillary tube system for embryo transfer of animals.

Further, according to the invention a gynecological mirror device, in particular animal vaginal speculum device is provided, wherein the gynecological mirror device comprises an angled forceps, wherein the angled forceps comprises two leg sections each comprising an end portion, wherein the longitudinal axis of the end portion forms an angle with the corresponding longitudinal axis of the leg section of the forceps, and wherein an inner surface of the end portion is configured to form a flat surface.

In an embodiment of the invention an outer surface of the end portion is provided with at least one groove and/or wherein the forceps comprises a slot at transition between the leg portion and the end portion. The at least one groove and the slot have the advantage that for example an unintentionally leap out or slip out of an animal vagina to be investigated can be prevented.

The embodiments herein will be described and explained with additional specificity and detail through the use of the accompanying drawings in which:

Fig. 1 is a perspective view of a system according to an embodiment of the invention;

Fig. 2 is a perspective view of the stand device of the system of Fig. 1 ;

Fig. 3a is a perspective view of the fixation device of the system of Fig. 1 ;

Fig. 3b, c, d are perspective views of the fixation device of Fig. 3a, wherein a mouse is received and fixed as example for a small animal;

Fig. 4 is a detail view of a lower end portion of the fixation device of Figs. 1 and 3a-d;

Fig. 5 is a detail view of an upper end portion of the fixation device and one of the holding elements and closing means;

Fig. 6 is a detail view of the slot and the hip fixation units of the fixation device of Figs. 1 and 3a-d to 6; Fig. 7 is a perspective view of a gynecological mirror device;

Fig. 8 is a perspective view of a t capillary and a transparent adapter;

Fig. 9 is a perspective view of the transparent capillary and the transparent adapter of

Fig. 8 after assembly;

Fig. 10 is a detail view of the transparent capillary and the transparent adapter of Fig. 9;

Fig. 11 is a further detail view of the connection of the transparent capillary and the transparent adapter of Figs. 9 and 10; and

Fig. 12 is a detail view of the outer end of the transparent adapter.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

In Fig. 1 a perspective view of a system 1 comprising a stand device 2, in particular a gynecological stand device, and a fixation device 3, in particular an animal fixation device, preferably a rodent fixation device, according to an embodiment of the invention is shown. Further, in Fig. 2 the stand device 2 and in Fig. 3a the fixation device 3 of the system 1 of Fig. 1 are each illustrated in a perspective view. The fixation device 3 is adapted to hold a smaller object, preferably a small animal, e.g., a rodent, in a predefined position, in particular a position suitable for allowing access, e.g., to the genital tract or vagina of a female animal. Such system 1 is in particular configured for a process of a non-surgical embryo transfer from said animal or to said animal. However, the invention is not limited thereto. In Figs. 3b to 3d a mouse is received in the fixation device 3 as an example.

Furthermore, in Figs. 4, 5 and 6 parts of the fixation device 3 of Figs. 1 and 3a-d are illustrated in perspective views. The views of Figs. 1 to 6 are purely schematic and not drawn to scale. In particular the dimensioning of the stand device 2 and the fixation device 3 depends on the object, in particular animal, to be investigated and its size is therefore depends on the object to be investigated.

The stand device 2 comprises a housing 4, wherein the housing 4 comprises a front wall 5, which is provided with an opening 6 to direct light through the opening 6. The housing 4 is further provided with a lighting device 7 which is arranged within the housing 4 as shown in the figures to direct light through the opening 6 to the outside of the housing and to the object to be investigated, held in the fixation device 3 and positioned in the stand device 2.

However, in an alternative embodiment the lightning device 7 can be also directly received or attached, releasably attached or fixedly attached in the opening 6 of the housing 4 (not shown). The lightning device 7 is in particular used for trans-abdominally directed light used for visualization of the female genital tract of an animal to be investigated, e.g. a mouse 58 as shown in Figs. 3a-3d. The lighting device 7 comprises at least one lighting element 8 such as, e.g., an Light-emitting diode (LED) or an LED-array etc. However, the invention is not restricted to LED(s) as lightning element(s). Any other lightning element or combination of lightning elements can be used as well which is/are suitable to be arranged in the housing 4 and to direct light through the opening 6 in the front wall 5 to illuminate the object or a part of the object to be investigated, in particular a low abdomen 59, e.g., the genital tract, including vaginal area, of an animal, e.g., mouse 58, to be investigated. Optionally the stand device 2 can comprise in addition to the lightning device 7 at least one optical element (not shown) such as for example a mirror and/or lens to control the light of the lightning device, e.g., for focusing or scattering the light depending on the intended function or use, in particular an intended visualization etc.. In general, the illumination of, e.g., a mouse genital track as show for example in Figs. 3c and 3d, is happening by directing a lightning element 8 (e.g., an LED element) (touching) to mouse abdominal area 59. Therefore it can be advantageous to adjust light (e.g. LED light) directly touching mouse fur. While opening vagina 57 with the gynecological mirror device (as shown and explained with respect to Fig. 7 below) an operator can clearly observe under binocular microscope the vaginal area 57 and entrances into uterus horns. In this case optionally at least one or more further optical elements can be applied.

In the embodiment as shown in Figs. 1 and 2 the lightning device 7 is at least movably arranged within the housing 4, for example toward and away from the opening of the housing at the front wall as indicated by arrow 9. In an embodiment the lightning device 7 is configured to be rotatable as indicated by arrow 10. Moreover and not shown in the figures, the lightning device 7 located within the housing can be also configured to be movable upwards and downwards within the housing in addition or instead of rotating the lightning device 7.

The housing 4 comprises a guide slot 11 in at least one or both (not shown) of its sidewalls 12 along which the lightning device 7 is movably arranged toward and away or forth and back from the opening 6 in the front wall 5 of the housing 4. The lightning device 7 is attached to an actuation device 13, which is movably received in the guide slot 11 to move the lighting device 7 toward and away from the opening 6. Further, the actuation device 13 can be optionally further rotatably to rotate the lightning device 7 connected with the actuation device 13.

In the embodiment as illustrated in Figs. 1 and 2, the actuation device 13 comprises a shaft 14 movably received within the guide slot 11 or guide slots to move the shaft 14 and thus the lightning device 7 along the corresponding guide slot(s) 11 toward and away from the opening 6 in the front wall 5 of the housing 4. In an embodiment, the shaft 14 is a cylindrical shaft 14 and optionally further rotatably around its longitudinal axis 15 for rotating the lightning device 7 connected with the shaft 14. As shown in Figs. 1 and 2 the shaft 14 can comprise an additional handle element 16 or handle portion at its outer end, to allow an easier actuation of the shaft 14. As mentioned before the shaft 14 is moved together with the lightning device 7 along the guide slot 11 toward and away from the opening 6 in the front wall 5 of the housing 4 and in a preferred embodiment the shaft 14 together with the lightning device 7 is optionally further rotatable around the longitudinal axis 15 of the shaft 14 if required. The shaft 14 and in particular its optional handle element 16 can be operated manually. In the embodiment as shown in Figs. 1 and 2 the shaft 14 is provided optionally with an additional stability element 17, e.g., a disc element, next to the side wall of the housing 4 which is configured and positioned on the shaft 14 adjacent the inner surface of side wall 11 of the housing 4 to avoid an unintended tilting of the shaft 14 within the corresponding guide slot 11 when the shaft 14 is moved along the guide slot 11. Such stability element 17 is in particular suitable when the housing 4 comprises only one guide slot 11 instead of two guide slots 11 in each of its opposite side walls in which the shaft 14 is received.

However, the invention is not restricted to a manual operation of the actuation device 13 and in particular the shaft 14. Moreover, the invention is not limited to the configuration of the actuation device 13 as described. Instead any actuation device or combination of actuation devices can be provided which is/are suitable to allow at least movement of the lightning device 7 toward and away from the opening 6 in the front wall 5 of the housing 4 and preferably an additional rotatability of the lightning device 7.

As mentioned before at least one additional optical element (not shown) can be provided. Said at least one optical element can be either fixedly attached to the housing 4 or the at least one optical element can be movably and/or rotatably arranged together with the lightning device 7 and its actuation device 13 or independent thereof within the housing 4 depending on the intended purpose or use. The stand device 2 as shown in Figs. 1 and 2 is further adapted to position the fixation device 3 and to hold the fixation device 3 in position, in particular so that the fixation device 3 cannot move within the stand device 2 unintentionally.

As shown in Figs. 1 and 2, the stand device 2 comprises a receiving and holding unit 18. In the embodiment as shown in Figs. 1 and 2 the receiving and holding unit 18 comprises at least one or a plurality of ribs 19, which are arranged on the outside of the outer wall 5 of the housing 4 to receive the fixation device 3 in between and to hold the fixation device 3 in position in particular in position in front of the opening 6 of the front wall 5. Furthermore, the receiving and holding unit 18 can comprise an additional receiving and holding section 20 comprising a base portion 21 provided with at least one or a plurality of ribs 19. The base portion 21 is attached to the housing 4, i.e. the front wall 5 of the housing 4, as a separate part or forms an integral part of the housing 4 as shown in the embodiment illustrated Figs. 1 and 2. Further, the base portion 21 forms an angle b with the housing 4. Angle b is chosen, so that when the fixation device 3 is positioned and held in its final position in the stand device by the receiving and holding unit 18 as shown in Fig. 2, the fixation device with the part of the object to be investigated, in particular the genital tract of an animal, is positioned in front of the opening 6 of the housing 4. Thus, light of the lightning device 7 positioned behind the opening 6 of the housing can be directly directed to the part of the object to be investigated. Therefore optimal conditions for investigation of an animal and in particular its genital tract can be provided. In the embodiment as shown in Figs. 1 and 2 the angle b is for example 90°. However, any other value for angle b can be suitable as well depending on the design and form of the fixation device and its positioning in the stand device and the final position of the object, in particular animal, in the fixation device when investigated.

In the embodiment as shown in Figs. 1 and 2 one rib 19 is provided on the base portion 21 to receive a lower end 22 of the fixation device 3. The rib 19 forms for example a stop for the lower end 22 of the fixation device 3. Furthermore, the base portion 21 can be provided with two additional ribs 19 between which the fixation device 3 is received as shown in Figs. 1 and 2. In a further embodiment the three ribs 19 illustrated in Figs. 1 and 2 can be connected with each other to form a single frame (not shown) in which the fixation device 3 is received. In a further embodiment at least one of the ribs 19 of the receiving and holding unit 18 can be configured as latching element or snap-in element to provide a snap-in connection (not shown) between the rib 19 and the fixation device 3. However, the invention is not limited to the specific embodiments of the receiving and holding unit 18 and ribs 19 as described and illustrated in Figs. 1 and 2. Any other receiving and holding unit or combination of receiving and holding unit can be provided which is/are suitable to hold and fix the fixation device on the stand device in a predefined or final position which allows investigation of an object in particular an animal and preferably the genital tract of the animal.

As shown in Figs. 1 and 3a-3d, 4 to 6, the fixation device 3 comprises a tubular housing 23 in which the object to be investigated, in particular an animal, e.g. a small animal such as a mouse 58, a rat, a guinea pig etc., is received. The tubular housing 23 is for example L- shaped or C-shaped.

The tubular housing 23 comprises an upper end 24 and a lower end 26. The upper end 24 of the tubular housing 23 is provided with an opening 25, e.g. a slot as show in Figs. 1, 3 and 6. The tubular housing 23 is received in the receiving and holding unit 18 of the stand device 2, wherein the opening 25 of the tubular housing 23 is positioned adjacent the opening 6 at the front wall 5 of the housing 4, when the fixation device 3 is held in the stand device 2 in its predetermined or final position for investigation of an object, in particular animal. The object to be investigated such as an animal, e.g. mouse 58, is received within the tubular housing 23 of the fixation device 3. The head of the animal to be investigated is positioned at the lower end 26 of the tubular housing 23 as shown in Figs. 3b-d. The part to be investigated of the animal, e.g. the genital tract 57, abdomen 59 or body of the animal, is positioned at the opening 25 at the upper end 24 of the tubular housing 23 and adjacent or preferably directly in front of the opening 6 in the front wall 5 of the housing 4. In other words the opening 25 of the tubular housing 23 is positioned in front of the opening 6 of the front wall 5 of the housing 4 as shown in Fig. 1. Thus, a very good illumination of the part of the animal to be investigated can be achieved

At the upper end 24 of the tubular housing 23 additional holding elements 27 for the paws 60 or legs of the animal to be investigated can be provided as shown in Figs. 1, 3a-d, 5 and 6. The tubular housing 23 is provided with two slots 28 as holding elements 27 to receive and hold the paws or legs of the animal to be investigated. The slots 28 can be provided with an additional foam or rubber layer to increase comfort for the animal, e.g., mouse 58, to be investigated. Further, in the embodiment as shown in Figs. 1, 3a-d and 5, on each side of the slot 28 the tubular housing 23 can be provided with an additional protruding portion 29 which is configured to attach a closing means, e.g. an elastic ring 30 or cover, to close and lock the open end of the slot 28, when the paw 60 or leg of the animal is received in the slot 28. Thus, the animal cannot remove its paws 60 or legs out of the slot 28 during investigation. However, the invention is not limited to said particular configuration of a holding element 28. Instead any holding element can be provided which is suitable to receive and hold the paws or legs of an animal to be investigated in position and preferably prevents and unintended removal of the corresponding paw or leg of the animal.

As shown in Figs. 1, 3 and 6, the opening 25, e.g. slot, of the tubular housing 23 is large enough to allow access to the region of the object to be investigated, in particular the genital region, in particular female tract or vagina 57 of an animal, e.g., mouse 58, to be investigated. The opening 25 of the tubular housing 23 allows to position the lightening device 7 directly in front of the part of the animal to be investigated and in particular directly in front of the genital tract area corresponding to low part of animal abdomen.

Further, as shown in Figs. 1, 3a-3d and 4, the tubular housing 23 can be provided with an additional head fixation unit 31 for fixing and preferably positioning the head 61 of the animal (see Figs. 3b. d) to be investigated in the tubular housing 23. The head fixation unit 31 comprises a head receiving element 32, in particular an elastic and/or flexible head receiving element 32 made of, e.g., a rubber material and/or foam material. The head receiving element 32 is preferably additionally movable along the tubular element 23 to adapt the position of the head receiving element 32 according to the intended position of the head of the animal within the tubular housing 23. Further, the head receiving element 32 is preferably removable from the tubular housing 23 if required, e.g. to insert an animal through the lower or upper end 26, 24 of the tubular housing 23 into the tubular housing 23. The head receiving element 32 as shown in Figs. 1, 3a-d and 4 is for example a lid with a hole and is made of a soft material such as foam material and/or rubber. An animal, e.g., mouse 58, can be inserted through the lower end 26 while puling up a tail via slot 44. However, there is also a possibility to insert an animal via opening 24 (25).

The head fixation unit 31 further comprises at least one actuation element 33 to fix and hold the head receiving element 32 in position, when the head 61 of the animal, e.g. mouse 58, is received in the head receiving element 32 and further to release the head receiving element 32, e.g., to remove the head receiving element 32 from the tubular housing 23 and thus the animal after investigation of the animal. In Figs. 1, 3a-d and 4 the actuation element 33 is a pin 34 which comprises a thread section 35 and optionally an additional handle element 16. The pin 34 is received with its thread section 35 in a corresponding thread hole 36 of the tubular housing 23. To fix and hold the head receiving element 32 in position the pin 34 is screwed into the tubular housing 23 and its thread hole 36 to contact the head receiving element 32 and to be preferably pressed against the head receiving element 32 to hold and fix the head receiving element 32. To release the head receiving element 32 the pin 34 is unscrewed to move the pin 34 out of contact with the head receiving element 32. However, the invention is not restricted to the head fixation unit 31 and the actuation element 33 as shown in the figures. Any other head fixation unit 31 and actuation element 33 can be provided which are suitable to hold the head of an animal to be investigated in a fixed position.

In the embodiment as shown in Figs. 1, 3a-d and 6, the tubular housing 23 can be provided with at least one additional hip fixation unit 37 for fixing and preferably positioning the hip region of the animal within the tubular housing 23. In Figs. 1, 3a-d and 6 two hip fixation units are provided on opposite sides of the tubular housing 23 to contact the hip region of the animal within the tubular housing 23 from the two sides. Each hip fixation unit 37 comprises a hip receiving element 38 and an actuation element 39. In the embodiment as illustrated in Figs. 1, 3a-d and 6, the actuation element 39 is releasably or fixedly connected with the hip receiving element 38. The hip receiving element 38 is for example an elastic and/or flexible hip receiving element which is made, e.g., of a rubber material and/or foam material. The hip receiving element 38 is further preferably plate shaped or adapted to the contour of the animal body to fix the animal body in its hip region, namely at its hips, or above its hips or below its hips.

The actuation element 39 of each hip fixation unit 37 fixes and holds the hip receiving element 38 in position, when the hip region of the animal is received in the hip receiving element 38 and further to release the hip receiving element 38, e.g., to remove the hip receiving element 38 from the animal after investigation. After removing the hip receiving element 38 from the animal, the animal can be withdrawn from the lower or upper end 26, 24 of the tubular housing 23. In Figs. 1, 3a-d and 6 the actuation element 39 is also a pin 40 which comprises a thread section 41 and preferably an additional handle element 42. The pin 40 is received with its thread section 41 in a corresponding thread hole 43 of the tubular housing 23. To fix and hold the hip receiving element 38 in position the pin 40 is screwed into the tubular housing 23 and its thread hole 43 together with the hip receiving element 38 until the hip receiving element 38 contacts the animal in the hip region of the animal to hold and fix the animal in its hip region in an intended position to investigate the animal. After investigation of the animal the pin 40 is unscrewed until the hip receiving element 38 is out of contact with the hip region of the animal, e.g., to remove the animal from the tubular housing 23.

The tubular housing 23 is provided along its length with an opening, e.g., a slot 44 or groove as shown in the embodiment in Figs. 1, 3a-d and 4. The slot 44 extends in the embodiment as illustrated in Figs. 1, 3a-d and 4, e.g., along the entire length of the tubular housing 23 and is therefore open at its both ends. However, the slot 44 can be also for example closed at one or both of its ends. Further, the fixation device 3 can comprise optionally at least one tail fixation element 45 which is receivable within the slot 44, preferably at a position adjacent the tail of the animal. Thus, the tail of the animal cannot move unintentionally beyond the tail fixation element 45 during investigation of the animal. Preferably, two tail fixation elements 45 are arranged in the slot 44 on each side of the animal tail to position and hold the tail in between. Each tail fixation element 45 is for example elastic and/or flexible, so that the tail fixation element 45 can be compressed to insert the tail fixation element 45 into the slot 44. After insertion, the tail fixation element 45 expands again and can be therefore held in position within the slot 44. The tail fixation element 45 is made, e.g., of rubber and/or a foam material. Further, the tail fixation element 45 can be a metal spring (not shown) as well and thus made of metal. Furthermore, the tail fixation element 45 can be a plastic and/or metal plug which is insertable into the slot 44 of the tubular housing 23, wherein the tubular housing 23 is flexible and/or elastic to allow insertion and holding of the plug. However, the invention is not restricted to the examples of tail fixation elements 45. Any kind of tail fixation element or combination of tail fixation elements can be provided which are suitable to prevent an unintentional movement of the tail of an animal received in the tubular housing.

The tubular housing 23 is preferably made of a transparent material or semi-transparent material. However, the tubular housing 23 can be made of an opaque material as well. In particular the tubular housing is made of, e.g., at least one plastic material such as for example thermoplastic material, thermosetting plastic, and/or elastomer. The tubular housing 23 can be further flexible and/or elastic or alternatively rigid. Principally the tubular housing 23 can be also made of metal. Moreover, dependent on the animal received in the tubular housing 23 additional openings (not shown) in the tubular housing 23 can be provided to allow further air exchange if required.

In Fig. 7 a perspective view of a gynecological mirror device 46 is disclosed to be used as additional and optional component together with the stand device 2 and the fixation device 3 of the system 1 described before with respect to Figs. 1 to 6.

The mirror device 46 comprises an angled forceps 47 or angled tweezers. In the following the term forceps is used. However, the term tweezers can be used as well. The forceps 47 comprises two leg sections corresponding end portions 48. The two end portions 48 of the forceps 47 form an angle with the leg sections. In this connection an angle a in a range between preferably 60° to 140° is provided between the longitudinal axis 49 of the end portion 48 and the corresponding longitudinal axis 50 of the leg section of the forceps 47. The longitudinal axis 49 of each end portion 48 is indicated with a dashed line and the corresponding longitudinal axis 50 of the leg section of the forceps 47 is indicated with a dash-dotted line. The outer surface 52 of each end portion 48 is provided with deepenings, e.g., grooves 53. Said grooves 53 prevent an unintended slip out, e.g., form the vagina of an animal to be investigated. In addition or instead of the grooves 53 a slot 54 is provided at the transition between the leg sections of the forceps 47 and the corresponding end portions 48. The slot 54 also prevents that the end portions 48 with their mirror surface unintentionally leap out or slip out of the animal vagina.

Further, in Figs. 8 and 9 a perspective view of a transparent adapter 55 and a transparent capillary 56 are shown which are in particular suitable for non-surgical embryo transfer procedures using the gynecological mirror device shown in Fig. 7 and the stand device and the fixation device described before with respect to Figs. 1 to 6. In Fig. 8 the transparent capillary 56 and the transparent adapter 55 are shown independent from each other while in Fig. 9 the transparent adapter 55 is attached on the corresponding end of the transparent capillary 56 for investigation of an animal and in particular for embryo transfer.

Since the adapter 55 and the capillary 56 are transparent loading of embryos can be reliably monitored and controlled during, e.g., a transfer of embryos into pseudopregnant female animals, in particular small size mammals, for example mice etc.. The preferably transparent adapter 55 and capillary 56 form additional and optional components of the system described before with respect to Figs. 1 to 6 and 7.

In Figs. 10, 11 and 12 further details of the transparent adapter 55 and the transparent capillary tube 56 are illustrated in enlarged perspective views. The transparent adapter 55 is preferably made of at least one transparent elastic and/or flexible material, e.g., at least one transparent elastic plastic material and/or transparent flexible plastic material. Since the transparent adapter 55 is elastic and/or flexible the handling is easier when investigating an object such as an animal and in particular when transferring embryos of such an animal. However, the transparent adapter 55 can be also made of transparent glass.. The adapter 55 and/or capillary tube 56 can be made of a transparent plastic material such as, e.g. transparent silicone, transparent Low Density Polyethylen (LDPE) or other non-toxic similar transparent materials.

As shown in Fig. 12 an example of a suitable internal diameter of the adapter 55 is, e.g., di = 0,28mm. Further, an example of a suitable external diameter of the adapter 55 is, e.g., de = 0,61mm. In general size of blastocysts is in a range between 0.1mm - 0.2mm, a suitable internal diameter di of the adapter 55 is preferably in a range between di: 0.08mm to 2.5mm and a suitable external diameter de of the adapter 55 is preferably between de: 0.1mm to 3.5mm.

The system comprising at least the stand device and the fixation device and in preferred embodiments further comprising or using additional and optional components, i.e., the gynecological mirror device, the transparent capillary and transparent adapter for efficient non-surgical transfer of embryos into pseudopregnant female animals, in particular small size mammals, for example mice etc.

The system and its components can be used for animal immobilization and efficient transfer of mouse embryos into uterine horn(s) due to the visualization by trans-abdominally focused light of the female genital tract from vulva to the cervix uteri. The system and its components can efficiently and cost-effectively replace standard surgical embryo transfer procedures.

Further, the system and its components can be applied for the standard embryo transfer procedures during pathogen free import of mouse lines, in vitro fertilization (IVF), strain maintaining, transfer or recovery of cryopreserved embryos procedures of wild type animals, e.g., mouse, rat, etc., or transgenic and gene modified animal models. In addition, the system and its components can be successfully applied for transfer of microinjected, electroporated, transfected, etc. embryos obtained from direct genome editing procedure using, as example, transgenic systems or sequence specific programmable nuclease ZFN (Zink-Finger Nucleases), TALEN (Transcription Activator- Like Effector Nucleases), CRISPR/Cas9, CRISPR/Cpfl and etc.. Hence, the system and its components are applicable for transfer of wild type, transgenic and genetically modified embryos including stem cell-containing chimeric blastocysts.

Further, the system and its components do not require or in other words exclude the surgery procedure, hence, recipient female animals do not have to be anesthetized and suffer from the surgical procedure side effects. The system and its components eliminate a painful surgical procedure. Moreover, the system and its components also exclude potential complications associated with application of the anaesthesia as well as with post-surgical recovery and care. In particular, the system and its components reduce the technical expertise and personal qualification necessary for surgical embryo transfer, anesthesia, and simplify authority approval of the embryo transfer procedure. Collectively the system and its components provide an efficient and technically simplified alternative to surgical embryo transfer. Nowadays, genetic animal modeling and gene editing technologies became a powerful tool for medical and bio-pharmacoloical research to investigate molecular bases of diseases and to discover drug and biopharmaceutical components for its effective treatment. The establishment of animal models in general (mouse, rat models in particular) to study the potential functional roles of genes and their products in human diseases is an important aspect of biomedical studies.

The system and its components intend to solve problems in particular associated with surgical as well as current non-surgical embryo transfer procedures.

Using the system does not require surgery, therefor there is no need for the anesthesia, analgesics and post-surgical recovery and care. The use of the stand device and the fixation device of the system is further simple and does not require special expertise and authorizations. The same applies to the other components of the system, i.e. the gynecological mirror device, the transparent capillary and transparent adapter.

The system and its components drastically improves non-surgical embryo transfer procedure and provide suitable devices for animal immobilization, for visualization of the female genital tract (from vulva to the cervix uteri), for opening the vagina of the recipient female animal, for precise embryo collection and visually controlled embryo transfer into uterine horn.

The system and its components therefore allow an animal immobilization, which guaranties painless of embryo transfer. Further, a control of embryo transfer procedure using operation microscopy and trans-abdominally directed electrical light (preferably LED as lightning device of the stand device) visualize the female genital tract that results in precise embryo delivery into the entry of uterine horn(s). Due to visualization of the procedure when using the system and its components, an embryo transfer into both uterine horns of the same recipient female animal is fast and reliable. The gynecological mirror device of the system further allows easy and painless opening of the vagina of the recipient female animal. Moreover, the transparent capillary or in other words transparent pipet and the transparent adapter or in other words transparent extender allows the direct visual control of the embryo collection and precise painless transfer without losing of embryos.

The system and its components therefore result in precise embryo collection and further an efficient embryo transfer. Thus a high percentage of pregnancy of animals comparable to current surgical procedures can be achieved. Further, the number of donor animals can be decreased that are needed for a given experiment and the number of preudopregnant recipient female (foster) mammals can be reduced. Furthermore, the use of the system and its components does not require qualified experienced personal for surgical manipulation. Moreover, overall cost of the embryo transfer can be reduced.

The system is in particular suitable for non-surgical embryo transfer procedures and can be used for a non-surgical embryo transfer method, wherein trans-abdominally applied electric light for visialization of female animal genital tract can be applied by the stand device of the system. The standard lightening procedures, accompanied by the microscopy is not sufficient because of the ultra low opening of the animal vagina.

The system therefore provides a gynecological stand device and animal fixation tube, i.e. the fixation device. The gynecological stand device is configured to hold the fixation device, i.e. an animal fixation tube, preferably under an angle that allows to position animal vagina upright under an objective of the operation microscope.

In addition the lightning device of the stand device provides an electric light element (preferably LED) and thus a suitable illumination device can be incorporated into the gynecological stand. Said lightning device is located in the upper part of the stand device as illustrated in Figs. 1 and 2 and thus positioned, directly to a genital tract corresponding to low part of animal abdominal area. This allows visualizing a female genital tract from vulva to the cervix uteri under an operating microscope when animal is placed in the fixation device and its tubular housing positioned in the gynecological stand device. Notably, the opening or slot of the tubular housing is preferably exactly in the region where the lightning device of the gynecological stand device is placed, allowing the light beam to be directed trans- abdominally directly to a genital tract.

The gynecological mirror device of the system allows easy and painless opening of the vagina of the recipient female animal during embryo transfer procedure, and stay it open. The gynecological mirror device further permits visualizing of genital tract and input the whole into uterine horns under operation microscope and further a controlled delivery of transferred embryos to the uterine horns by the transparent capillary or pipette provided with the transparent adapter or extender. The transparent capillary or pipette has the advantage that the trans-abdominal lightning permits visualizing embryos within the transparent capillary or pipette and allows its direct control. The flexible and/or elastic transparent adapter positioned at the end of the transparent capillary tip protects, e.g., an animal from been hurt by the capillary. The system and its components can be applied for the standard embryo transfer procedures during animal line importation, strain maintaining, transfer or recovery of cryopreserved embryos of wild type, transgenic animals, and gene modified animal models (preferably rodents -mice, rats, etc). In addition, the system and its components can be successfully applied for transfer of microinjected, electroporated, transfected, etc. embryos obtained from genome editing procedures. The system and its components are also applicable for transfer of stem cell-containing chimeric blastocysts. In particular, the system provides the combination of the gynecological stand device and animal fixation device which is particularly suitable for non-surgical embryo transfer procedure in mammals, especially rodents such as mice, rats, guinea pigs, etc. and other relatively small size animals.

The embodiments of the system and its components as described above with respect to Figs. 1 to 12 can be combined with each other and in particular single features thereof.

List of reference signs System Stand device Fixation device Housing (of stand device) Front wall Opening Lightning device Lightning element Arrow Arrow Guide slot Side wall (of housing) Actuation device Shaft Longitudinal axis (of shaft) Handle element Stability element Receiving and holding unit Rib Receiving and holding section Base portion Lower end (of fixation device) Tubular housing Upper end (of tubular housing) Opening (of tubular housing) Lower end (of tubular housing) Holding element Slot Protruding portion Elastic ring Head fixation unit Head receiving element Actuation element Pin Thread section Thread hole Hip fixation unit Hip receiving element Actuation element Pin

Thread section Handle element Thread hole Slot

Tail fixation element Gynecological mirror device Forceps

End portion (of forceps)

Longitudinal axis (of end portion)

Longitudinal axis (of forceps)

Inner surface

Outer surface

Groove

Slot

Adapter

Capillary

Vagina

Mouse

Mouse abdominal area paw head

Claims

1. System (1) comprising a gynecological stand device and a fixation device (3) configured to receive and hold an animal to be investigated in position, wherein the stand device (3) comprises a housing (4) provided with a lighting device (7), and wherein the fixation device (3) is releasably attached to the stand device (2) in a position in which light of the lighting device illuminates a genital tract of the animal received in the fixation device (3).

2. The system of claim 1, wherein the stand device (2) comprises an opening (6) at a front wall (5) of the housing (4) in which the lighting device (7) is directly received or wherein the lighting device (7) is movably arranged within the housing (4) in a direction toward and away from the opening (6), wherein the lighting device comprises preferably at least one lighting element (8) and wherein the lighting element is in particular an LED or an LED-array.

3. The system of any of the preceding claims, wherein the lighting device (7) is rotatably arranged within the housing (4).

4. The system of any of the preceding claims, wherein the stand device (2) comprises at least one optical element, preferably a lens and/or mirror.

5. The system of any of claims 2 to 4, wherein the stand device (2) comprises an actuation device (13) which is connected with the lighting device (7) to move the lighting device at least in the direction toward and away from the opening (6) in the front wall of the housing (4) and/or to rotate the lighting device (7), wherein the actuation device (13) preferably comprises a shaft (14) which is connected to the lighting device and movably received within at least one guide slot (11) provided in a corresponding side wall (12) of the housing (4), wherein the shaft is movably arranged along the guide slot (11) together with the lighting device toward and away from the opening in the front wall of the housing and/or rotatable around its longitudinal axis (15).

6. The system of any of the preceding claims, wherein the stand device (2) comprises a receiving and holding unit (18) for receiving and holding the fixation device (3) in the position in which light of the lighting device (7) illuminates an area of the object to be investigated and received in the fixation device (3), in particular a genital tract of an animal received in the fixation device.

7. The system of any of the preceding claims, wherein the fixation device (3) comprises a tubular housing (23) to receive the object to be investigated, wherein the tubular housing (23) preferably comprises at least one head fixation unit (31), at least one hip fixation unit (37) and/or at least one tail fixation element (45).

8. The system of claim 7, wherein the at least one head fixation unit (31) comprises a head receiving element (32), in particular a lid, and at least one actuation element

(33) to fix the head receiving element in position within the tubular housing, wherein the actuation element (33) is configured to be movable in contact with the head receiving element (32) to hold and fix the head receiving element in position and further movable out of contact with the head receiving element to release the head receiving element, wherein the actuating element (33) preferably comprises a pin

(34), wherein the pin comprises a thread section (35) and wherein the tubular housing (23) comprises a corresponding thread hole (36) in which the pin with its thread section is received, wherein the pin with its thread section is screwed into the thread hole until the actuation element is in contact with the head receiving element to hold and fix the head receiving element in position.

9. The system of claim 7 or 8, wherein the at least one hip fixation unit (37) comprises at least one hip receiving element (38) and at least one actuation element (39) to fix the hip receiving element in position within the tubular housing (23), wherein the actuation element (39) is releasably or fixedly connected to the hip receiving element (38) and is configured to be movable together with the hip receiving element in contact with the hip region of an animal as object to be investigated to hold and fix the hip region of the animal in position and is further movable out of contact with the hip region of the animal to release the animal, wherein the actuation element (39) preferably comprises a pin (40), wherein the pin (40) comprises a thread section (41) and wherein the tubular housing (23) comprises a corresponding thread hole (43) in which the pin with its thread section is received, wherein the pin with its thread section is screwed into the thread hole until the hip receiving element is in contact with the hip region of the animal to hold and fix the hip region of the animal in position.

10. The system of any one of claims 7 to 9, wherein the tubular housing (23) comprises a slot (44) along its length, preferably along its entire length, and wherein the at least one tail fixation element (45) is configured to be insertable in the slot (44) and held in position when inserted in the slot.

11. The system of any one of the preceding claims, wherein the fixation device (3) comprises at least one holding element (27) to hold a paw of an animal as object to be investigated, wherein the holding element (27) is a slot (28) formed at an end, in particular an upper end (24), of the tubular housing (23) to receive the paw of the animal, wherein preferably on each side of the slot (28) the tubular housing is provided with an additional protruding portion (29) which is configured to attach a closing means, in particular an elastic ring (30) or cover, to close and lock the open end of the slot (28).

12. The system of any one claims 7 to 11 , wherein the tubular housing (23) comprises at its end, in particular the upper end (24), an opening (25) which is large enough to allow investigation of a part of the object to be investigated, in particular a part of an animal to be investigated, preferably the genital tract of the animal, and wherein the opening (25) of the tubular housing (23) is preferably positioned adjacent or in front of the opening (6) of the housing (4), when the tubular housing (23) is attached to the stand device (2), wherein the tubular housing (23) is preferably L-shaped or C- shaped, wherein the upper end (24) of the tubular housing (23) is in particular positioned in an upright position when attached to the stand device (2) in the position in which light of the lighting device (7) illuminates an area of the object to be investigated received in the fixation device (3), in particular a genital tract of an animal.

13. Capillary tube system to be used with the system of any one of the preceding claims, wherein the capillary tube system comprises a transparent capillary (56) and a transparent adapter (55), wherein the transparent adapter (55) is optionally releasably connectable with an end of the transparent capillary (56) and wherein the transparent adapter (55) is preferably flexible and/or elastic.

14. Mirror device (46), in particular gynecological mirror device to be used with the system of any one of the preceding claims, wherein the mirror device (46) comprises an angled forceps (47), wherein the angled forceps comprises two leg sections each comprising an end portion (48), wherein the longitudinal axis (49) of the end portion (48) forms an angle with the corresponding longitudinal axis (50) of the leg section of the forceps, and wherein an inner surface (51) of the end portion (48) is for example configured to form a flat surface and/or mirror surface.

15. The mirror device of claim 14, wherein an outer surface (52) of the end portion (48 is provided with at least one groove (53) and/or wherein the forceps comprises a slot (54) at transition between the leg portion and the end portion (48).