Methods for establishing and increasing a probability of fertlisation and pregnancy by insemination and devices for such methods

A mesoscale fluidic system with a cell permeable membrane and controlled parameters optimizes sperm sample preparation for IUI, IVF, or ICSI by increasing the number and quality of motile cells, addressing inefficiencies in existing sperm cell separation methods.

WO2026008118A1PCT designated stage Publication Date: 2026-01-08MOTILITYCOUNT
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Patent Information

Application Number
PCT/DK2025/050118
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2024-07-05
Filing Date
2025-07-04
Publication Date
2026-01-08

AI Technical Summary

Technical Problem

Existing methods for separating motile and non-motile sperm cells are inefficient, leading to insufficient motility and number of motile cells for optimal results in intrauterine insemination (IUI), in vitro fertilisation (IVF), or intracytoplasmic sperm injection (ICSI), with factors like health, genetics, morphology, temperature, and incubation time influencing sperm motility and number.

Method used

A mesoscale fluidic system with a cell permeable membrane separates motile and non-motile cells using a conditioning chamber and sample chamber, allowing motile cells to migrate through pores, with controlled parameters like temperature and incubation duration to increase the number of motile cells suitable for fertilization methods.

Benefits of technology

The system enhances the probability of successful fertilization and pregnancy by ensuring a sufficient number and quality of motile cells, providing early assessment and optimization of sperm samples for IUI, IVF, or ICSI.

✦ Generated by Eureka AI based on patent content.

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Abstract

The invention relates to a method and to a mesoscale device for establishing a probability of a sperm sample, from a selected one raw sperm sample of selected one mammal, being suitable for fertilisation and possibly pregnancy, the sperm sample comprising motile cells and non-motile cells. The invention also relates to a method and to a mesoscale apparatus for increasing a probability of a sperm sample, from a selected one raw sperm sample of selected one mammal, being suitable for fertilisation, the sperm sample comprising motile cells and non-motile cells.
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Description

[0001] METHODS FOR ESTABLISHING AND INCREASING A PROBABILITY OF FERTLISATION

[0002] AND PREGNANCY BY INSEMINATION AND DEVICES FOR SUCH METHODS

[0003] FIELD OF THE INVENTION

[0004] The invention relates to a method of estimating the quantity and quality of motile cells in a sperm sample and to a mesoscale fluidic system for increasing the number of motile cells in a sperm sample. The invention also relates to a method of establishing a probability of a sperm sample being suitable for at least one of intrauterine insemination (IUI), in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI), the sperm sample including both motile cells and non-motile cells. The invention also relates to a method of increasing the number of motile cells in a sperm sample including both motile cells and non-motile cells, particularly when using a mesoscale fluidic device comprising a cell permeable membrane between a control sample chamber for both motile cells and non-motile cells and a conditioning chamber for motile cells having passed the membrane by movement and migration themselves.

[0005] BACKGROUND OF THE INVENTION

[0006] The analysis for assessing a number and the motility of cells in a sperm sample may be performed by professionals in a laboratory environment. WO 2014 / 177157 discloses a system that can estimate the quantity of motile cells in a sample. The device of WO 2014 / 177157 has a sample chamber below a cell permeable membrane and a conditioning chamber above the cell permeable membrane. By applying a sperm sample below the cell permeable membrane, an efficient separation of motile cells from non- motile cells is provided.

[0007] However, even though a more efficient separation of motile cells from non-motile cells is obtained, there is still a possibility that the motility of the cells and the number of motile cells are not sufficient for obtaining optimal results in intrauterine insemination (IUI), in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). Various factors influence the motility of the sperm cells and the number of motile cells. Apart from defiant health and / or genetical deficiencies of the male from which the sperm sample is sampled, factors such as morphology, temperature and time of incubation for the motile cells to move from the sample chamber, through the cell permeable membrane to the condition chamber influence the motility of the cells and the number of motile cells, respectively. However, the probability of obtaining a pregnancy by intrauterine insemination (IUI), in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) is only established after an ovum being fertilised and implanted into a female mammal and only after some time thereafter establishing if pregnancy is obtained or not.

[0008] One object of the invention may be establishing, at an as early stage as possible before intrauterine insemination (IUI), in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI), establishing a probability of fertilisation and pregnancy.

[0009] Another object of the invention may be increasing a probability of a sperm sample with motile cells and non-motile cells being capable of fertilisation by intrauterine insemination (IUI), in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI).

[0010] Another object of the invention may be to obtain a certain number of motile cells before fertilisation is performed. Still another object may be to obtain as many motile cells as possible during a selected duration of time of incubation before fertilisation is performed.

[0011] SUMMARY OF THE INVENTION

[0012] One aspect of the invention generally relates to a method for establishing a probability of a sperm sample, from a selected one raw sperm sample of selected one mammal, being suitable for intrauterine insemination (IUI), in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI), the sperm sample comprising motile cells and non-motile cells, the method comprising the steps of:

[0013] - applying a conditioning medium for sperm cells to a conditioning chamber of the control mesoscale device via an inlet of the conditioning chamber, the conditioning chamber placed at an elevated position of the control mesoscale device,

[0014] - applying a first sperm sample comprising motile cells and non-motile cells from the selected one raw sperm sample of the selected one mammal to a sample chamber via a sperm sample inlet of the sample chamber, the sample chamber placed at a lowered position of the control mesoscale device,

[0015] - the sample chamber and the conditioning chamber being in fluid communication via pores in a cell permeable membrane, the cell permeable membrane having one surface facing the elevated position of the conditioning chamber and the cell permeable membrane having another surface facing the lowered position of the sample chamber,

[0016] - allowing motile cells in the first sperm sample to move by migration themselves from the lowered position of the sample chamber, through the cell permeable membrane, to the elevated position of the conditioning chamber during a selected incubation period for the motile cells to move. The one object of the invention may be obtained by

[0017] - applying a second sperm sample comprising motile cells and non-motile cells from the selected one raw sperm sample of the selected one mammal to a sample chamber of a mesoscale device via a sperm sample inlet of the sample chamber, the sample chamber of the mesoscale device being different to the sample chamber of the control mesoscale device,

[0018] - establishing at least one parameter of the motile cells having migrated from the sample chamber to the conditioning chamber through the cell permeable membrane of the control mesoscale device and controlling at least one parameter of the separation mesoscale device based upon the at least one parameter established in the control mesoscale device.

[0019] The control mesoscale device is useful in establishing if a sperm sample has a sufficient number of motile cells for a successful fertilisation and possibly pregnancy and / or if the motile cells have a good progressivity compared to non-motile cells for a successful fertilisation and possibly pregnancy and / or if the motile cells has a correct morphology for a successful fertilisation and possibly pregnancy.

[0020] Another aspect of the invention generally relates to a method for increasing the probability of a sperm sample, from the selected one raw sperm sample of selected one mammal, being suitable for intrauterine insemination (IUI), in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI), the sperm sample comprising motile cells and non-motile cells, and the method comprising the steps of:

[0021] - applying a conditioning medium for sperm cells to a conditioning chamber of a mesoscale device via an inlet of the conditioning chamber, the conditioning chamber placed at an elevated position of the mesoscale device,

[0022] - applying a sperm sample comprising motile cells and non-motile cells from the selected one raw spare sample of the selected one mammal to a sample chamber via a sperm sample inlet of the sample chamber, the sample chamber placed at a lowered position of the mesoscale device,

[0023] - the sample chamber and the conditioning chamber being in fluid communication via pores in a cell permeable membrane, the cell permeable membrane having one surface facing the elevated position of the conditioning chamber and the cell permeable membrane having another surface facing the lowered position of the sample chamber,

[0024] - allowing motile cells in the sperm sample in the mesoscale device to migrate themselves from the lowered position of the sample chamber, through the cell permeable membrane, to the elevated position of conditioning chamber during a selected incubation period for the motile cells to move. The other object of the invention may be obtained by

[0025] - controlling at least one of the following parameters during the incubation period: a temperature inside the sample chamber, a temperature inside the conditioning chamber, a duration of the incubation period, and

[0026] - where controlling at least one of the parameters during the incubation period is performed based upon parameters obtained from a sperm sample from the selected one raw sperm sample of the selected one mammal other than the sperm sample in the sample chamber of the mesoscale device.

[0027] The mesoscale apparatus is useful in obtaining sperm with an increased number of motile cells compared to non-motile cells for a successful fertilisation and possibly pregnancy.

[0028] In the present context, progressivity is a trajectory of motion that the sperm cells follow, whether it is a relative forward motion compared to non-forward, possibly in circles.

[0029] In the present context, incubation period is from when a sperm sample is applied to an inlet of a sample chamber to when motile cells are harvested for insemination.

[0030] BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Fig. 1 is a drawing of a control mesoscale device with a reference sample chamber, a sample chamber and a conditioning chamber, the reference sample chamber being viewed by microscope,

[0032] Fig. 2 is a drawing of the control mesoscale device with a reference sample chamber, a sample chamber and a conditioning chamber, an outlet of the conditioning chamber being viewed by microscope,

[0033] Fig. 3 is one drawing of the mesoscale device with a separation chamber comprising a control sample chamber and a conditioning chamber, the mesoscale device being placed in a temperature controlling incubator,

[0034] Fig. 4 is another drawing of the mesoscale device with a separation chamber comprising a control sample chamber and a conditioning chamber, the mesoscale device being placed in a temperature controlling incubator, and

[0035] Fig. 5A and Fig. 5B are drawings of parts of a mesoscale apparatus, the mesoscale apparatus comprising a control mesoscale device with a reference sample chamber, a sample chamber and a conditioning chamber and the mesoscale apparatus also comprising a separation mesoscale device with a sample chamber and a conditioning chamber.

[0036] DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION

[0037] Fig. 1 is a drawing showing one part of a control mesoscale device 1. The control mesoscale device is made from a transparent material, preferably plastic, more preferably a cyclic olefin copolymer, such as the product TOPAS'® COC from the company Topas Advanced Polymers. The part of the control mesoscale device has a reference sample chamber 2. The reference sample chamber 2 has a sperm sample inlet 3 and an air outlet 4. The reference sample chamber 2 is intended for a first raw perm sample being applied to the reference sample chamber 2 via the inlet 3. The control mesoscale device is placed in a measuring device for example a microscope or other apparatus for detecting physical parameters of a sample.

[0038] The reference sample chamber 2 is used for establishing a physical parameter such as a number, and / or a relatively high progression, and / or a morphology, of motile sperm cells and possibly also a number, and / or a relatively low progression, and / or morphology, of non-motile sperm cells of a raw sperm sample of a the one selected mammal, such as a human male, who's sperm sample is injected into the reference sample chamber 2 via the sperm sample inlet 3, for detection of one or more physical parameters.

[0039] Fig. 2 is a drawing showing another part of a control mesoscale device. The part of the control mesoscale device has a control chamber 5. The control chamber 5 has a sperm sample inlet 6 for a second raw sperm sample from the one selected mammal, and an air outlet 7. The control chamber 5 also has a motile sperm outlet 7 for motile sperm cells. Between the sperm sample inlet 6 of the control chamber 5 and the motile sperm outlet 7 of the control chamber 5, the control chamber 5 is divided into a sample chamber (not visible) and a conditioning chamber 9 (visible through a top of the control chamber 5, both provided inside the mesoscale device. The conditioning chamber 9 has a conditioning medium inlet 9. A conditioning medium in the conditioning chamber 9 allows the motile cells migrating themselves towards the motile cells outlet 7 and the conditioning medium may include nutrients for assisting the motile cells moving and migrating themselves towards the motile cells outlet 7.

[0040] The control chamber 5 comprises a motile cells passage 10 provided between the conditioning chamber 9 and the motile cells outlet 7. Motile cells from the conditioning chamber 9 will move and migrate themselves to the motile cells outlet 7 via the passage. Between the conditioning chamber 9 and the outlet 7, along the passage 10, observation of the motile cells additional to observation made in the reference sample chamber 2, may be performed to establish the number and / or the progressivity and / or the morphology of the motile cells in the passage 10.

[0041] The control chamber 5 comprises a cell permeable membrane (not visible) dividing the control chamber 5 into the sample chamber and the conditioning chamber 9. The cell permeable membrane has a plurality of pores each preferably having a cross-sectional area between 1 pm and 20 pm.

[0042] When the mesoscale device is in use, the control sample chamber is placed at lower position of the control mesoscale device compared to a position of the conditioning chamber, which is placed at an elevated position compared to the position of the control sample chamber.

[0043] The cell permeable membrane has a pore size allowing motile cells to move through the membrane. The cell permeable membrane is provided to ensure that cells are not transported from the control sample chamber to the conditioning chamber 9 via convection, so that cells present at in the conditioning chamber will only be motile cells that have traversed the cell permeable membrane by moving and migrating themselves through the pores of the membrane.

[0044] The control mesoscale device 1 is placed in an observation apparatus, for example a microscope, and the motile cells passage 10 is subjected to light from the microscope, as illustrated in the figure, for assisting possibly observing motile cells in the passage 10, by use of the microscope.

[0045] The reference sample chamber 2 is used for establishing a physical parameter such as the number and / or the progressivity and / or the morphology of motile cells in a first raw sperm sample of a selected one mammal. A second sperm sample from the same one raw sperm sample of the selected one mammal, preferably a male human, is injected into the sperm sample inlet 6 of the control sample chamber e. A number and / or a progressivity and / or a morphology of motile cells in the control chamber 5 is established, when viewed under the microscope.

[0046] When physical parameter such as the number and / or the progressivity and / or the morphology of both motile cells and non-motile cells in the reference sample chamber 2 has been established, and when possibly also the number and / or the progressivity and / or the morphology of only motile cells in the conditioning chamber 8 of the control chamber 5 have been established, during a selected duration of a incubation period for the motile cells to move through the cell permeable membrane, the number and / or the progressivity and / or the morphology of motile cells in the reference sample chamber 2 may be compared to the number and / or the progressivity and / or the morphology of motile cells in the conditioning chamber 8 of the control chamber 5.

[0047] If it is the number of motile cells being established, the concentration of motile cells in the reference sample chamber 2, that is, the number of motile cells compared to the number of non-motile cells, will be less than the concentration of motile cells in the conditioning chamber because in the conditioning chamber, only motile cells are present.

[0048] When the physical parameter such as the number of motile cells in the reference sample chamber 2 has been established, the sperm of the mammal may be established as suitable or non-suitable for at least one of the following fertilisation methods: intrauterine insemination (IUI), in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI), or the sperm of the mammal may be established as suitable for IUI, IVF or ICSI based upon empirically established data of the number of motile cells needed for fertilisation and possibly pregnancy.

[0049] If it is the number and progressivity of cells being established, the number of progressive cells in the reference sample chamber 2, that is, the number of motile cells having progress of moving along a relative forward trajectory compare to a non-forward trajectory, the number of progressive cells in the refence sample chamber may be higher than the number of progressive cells in the conditioning chamber because the overall number of motile cells in the refence chamber is higher than in the concentration chamber.

[0050] When the progressivity of motile cells in the concentration chamber has been established, the sperm of the mammal may be established as suitable or non-suitable for at least one of the following fertilisation methods: intrauterine insemination (IUI), in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI), or the sperm form the mammal may be established as suitable for IUI, IVF or ICSI, based upon empirically established data of when sperm cell is progressive or not. Based upon the data, an incubation protocol is established. The incubation protocol may be established by an algorithm based upon empiric data. Fig. 3 shows a mesoscale device 11 placed in an incubator. The mesoscale device 11 is a known device, preferably a mesoscale device as disclosed in WO 2014 / 177157, which is hereby incorporated by reference in the present application.

[0051] The mesoscale device has a separation chamber 12. The separation chamber 12 has a sperm sample inlet 13 and a motile cells outlet 14. Between the sperm sample inlet 13 and the motile cells outlet 14, the separation chamber 12 is divided into a sample chamber (not visible) and a conditioning chamber (visible from a top of the mesoscale device. The incubator 15 has a cavity holding the mesoscale device.

[0052] The separation chamber 12 comprises a cell permeable membrane (not visible) dividing the separation chamber 12 into the control sample chamber and the conditioning chamber. The sample chamber is provided at lower position of the mesoscale device compared to the conditioning chamber, which is placed at an elevated position compared to the sample chamber. One surface of the cell permeable membrane faces the lower position of the sample chamber and another opposite surface of the cell permeable membrane faces the elevated position of the conditioning chamber. The cell permeable membrane has a plurality of pores each having a cross-sectional area preferably between 1 pm and 20 pm, allowing motile cells to easily pass the cell permeable membrane and non-motile cells having difficulties passing the cell permeable membrane.

[0053] The cell permeable membrane has a pore size allowing motile cells to move through the membrane. The cell permeable membrane is provided to ensure that cells are not transported from the sample chamber to the conditioning chamber via convection, so that cells present at in the conditioning chamber will only be motile cells that have traversed the cell permeable membrane by moving through pores of membrane.

[0054] The incubator 15 has at least one cavity 16 for holding a mesoscale device. The cavity 16 has a bottom (not visible), sidewalls and a lid 17 for covering the mesoscale device when placed in the incubator 15. The lid 17 can be opened to allow a mesoscale device to be inserted into the cavity 16 of the incubator 15 and to allow a mesoscale device to be retracted from the cavity 16 of the incubator 15.

[0055] The incubator 15 is made from a material capable of heating the mesoscale device, the material being relatively easy to heat and being able to heat relatively fast, as example aluminium, when the incubator has a temperature higher than a temperature of the mesoscale device 11. Heating of the incubator 15 may be provided by a separate heating element intended for being placed in thermal contact with the incubator, or by heating elements incorporated into or onto the incubator 15.

[0056] Heating may be provided by any type of heating source suitable for the purpose and possibly known to the person skilled in the art, such as a separate heating element being solid or fluid and heating the incubator from outside the incubator, or a heated fluid flowing in ducts in or on the incubator. Alternatively, heating elements may be electrical heating elements heating the incubator from outside or from inside the incubator.

[0057] Fig. 4 show an incubator 15 with two cavities 16, each for holding a mesoscale device and each with a lid 17 capable of being open or closed. A separate heating element 18 is placed underneath a bottom of the incubator 15. The separate heating element 18 is heated by electrical heating. A top of the separate heating element 18 is in thermal contact with the bottom of the incubator 15. Heating of the separate heating element 18 is controlled in dependence of observations obtained from a mesoscale device, such as the mesoscale device shown in Fig. 1 and Fig. 2.

[0058] In the following, control of a mesoscale apparatus is described, the apparatus comprising a mesoscale device, a mesoscale device and a heating element.

[0059] Fig. 5A shows two parts of a mesoscale device as shown in fig. 1 and Fig. 2. Fig. 5B shows a mesoscale device as shown in Fig. 3 and Fig. 4.

[0060] An arrow A illustrates that one or more parameters observed in the mesoscale device is controlling one or more parameters of the mesoscale device.

[0061] Parameters observed in the mesoscale device may be a number of motile cells in the reference sample chamber 2, a number of motile cells in the control chamber, and a difference between the number of motile cells in the reference sample chamber 2 and the number of motile cells in the control chamber, said difference used for calculating a percentage between motile cells in the control chamber and motile cells in the reference sample chamber 2.

[0062] Parameters observed in the mesoscale device may additionally, or alternatively, be a the number of progressive cells in the conditioning chamber compared a number of nonprogressive cells in the control chamber, and a difference between the number of progressive cells in the conditioning chamber and the number of non-progressive cells in the control chamber, said difference used for calculating a percentage between motile cells in the control chamber and non-motile cells in the conditioning chamber.

[0063] Alternatively, only the number of progressive cells is counted, said number used as a number of motile cells in the conditioning chamber.

[0064] Parameters observed in the mesoscale device may additionally, or alternatively, be a the number of morphologically good cells in the conditioning chamber compared a number of morphologically poor in the control chamber, and a difference between the number of morphologically good cells in the conditioning chamber and the number of morphologically poor cells in the control chamber, said difference used for calculating a percentage between motile cells in the control chamber and non-motile cells in the conditioning chamber. Alternatively, only the number of morphologically good cells is counted, said number used as a number of motile cells in the conditioning chamber.

[0065] As described with reference to Fig. 1 and Fig. 2, a number and / or a progressivity and / or a morphology of both motile cells and non-motile cells may be established in the separation chamber of the mesoscale device. However, for control of one or more parameters of the mesoscale device, a number of only motile cells in the separation chamber needs to be counted and / or a progressivity of only motile cells in the separation chamber needs to be established and / or a morphology of only the motile cells in the separation chamber needs to be established.

[0066] A number, a progressivity and / or a morphology of at least motile cells is established in the control chamber of the mesoscale device. The number and / or the progressivity and / or the morphology of motile cells established in the reference sample chamber 2 may be compared to the number and / or the progressivity and / or the morphology of motile cells established in the control chamber. Based on empiric date, a probability of fertilisation / pregnancy and / or a fertilisation method and / or a fertilisation scheme is established. The probability of fertility and / or the fertilisation scheme established by the parameters of at least motile cells observed in the control chamber is used for controlling parameters of the mesoscale device.

[0067] One parameter of the mesoscale device to control is the temperature of the incubator and thus the temperature of the sample chamber and / or the conditioning chamber of the mesoscale device. Another parameter of the mesoscale device to control is a duration of an incubation period for the motile cells to move from the sample chamber to the condition chamber of the mesoscale device.

Claims

CLAIMS1. Method for establishing a probability of a sperm sample, from a selected one raw sperm sample of selected one mammal, being suitable for at least one of the following fertilisation methods: intrauterine insemination (IUI), in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI), the sperm sample comprising motile cells and non-motile cells, the method comprising the steps of:- applying a first sperm sample comprising motile cells and non-motile cells from a selected one raw sperm sample of a selected one mammal to a reference sample chamber of a mesoscale device via a sperm sample inlet of the reference sample chamber, and subjecting then reference sample chamber to analysis of at least one physical parameter indicative of a motility of the first sperm sample,- applying a conditioning medium for sperm cells to a conditioning chamber of a mesoscale device via an inlet of the conditioning chamber, the conditioning chamber placed at an elevated position of the mesoscale device, relative to a position of a control sample chamber of the mesoscale device, and- applying a second sperm sample comprising motile cells and non-motile cells from the selected one raw sperm sample of the selected one mammal to a control sample chamber, different from the reference sample chamber, via a sperm sample inlet of the control sample chamber, the sample chamber placed at a lowered position of the mesoscale device, relative to the position of the conditioning chamber,- the control sample chamber and the conditioning chamber being in fluid communication via pores in a cell permeable membrane, the cell permeable membrane having one surface facing the elevated position of the conditioning chamber and the cell permeable membrane having another surface facing the lowered position of the control sample chamber,- allowing motile cells in the second sperm sample to move by migration themselves from the lowered position of the control sample chamber, through the pores of the cell permeable membrane, to the elevated position of the conditioning chamber during an incubation period for the motile cells to move, and- establishing the at least one physical parameter of the motile cells in the reference sample chamber and, based upon the at least one physical parameter established in the reference sample chamber, selecting at least one parameter, different from the physical parameter established in the reference sample chamber, to control in at least one of the control sample chamber and the conditioning chamber, and the controlling the at least one parameter based upon the at least one physical parameter established in the reference sample chamber..

2. Method according to claim 1, where the at least one physical parameter of the motile cells in the reference sample chamber of the mesoscale device is selected from the following parameters: a number of motile cells, a progressivity of the motile cells, a direction of movement of the motile cells, a speed of movement of the motile cells, a morphology of the motile cells.

3. Method according to claim 1, where the at least one parameter of the separation chamber is selected from the following parameters:- a constant temperature during a period of time of at least one of the control sample chamber and of the conditioning chamber of the separation chamber,- a change of temperature over a period of time of at least one of the control sample chamber and of the conditioning chamber of the separation chamber,- a period of time of subjecting at least one of the control sample chamber and the conditioning chamber of the separation chamber to an elevated temperature compared to a temperature of the surrounding of the separation chamber,- a period of time of subjecting at least one of the control sample chamber and the conditioning chamber of the separation chamber to at least one of a temperature change or a number of temperature changes during the period of time.

4. Method according to any of the preceding claims, where,- if the physical parameter of motile cells in the first sperm sample is higher than an empirically established and selected physical parameter, the selected one raw sperm sample of the selected one mammal is determined suitable for at least one of the following fertilisation methods: intrauterine insemination (IUI), in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI), and- if the physical parameter of motile cells in the first sperm sample is lower than an empirically established and selected physical parameter, the selected one raw sperm sample of the selected one mammal is determined non-suitable for at least one of the following fertilisation methods: intrauterine insemination (IUI), in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI).

5. Method for increasing a probability of a sperm sample, from a selected one raw sperm sample of selected one mammal, being suitable for at least one of the following fertilisation methods: intrauterine insemination (IUI), in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI), the sperm sample comprising motile cells and non-motile cells, and the method comprising the steps of:- applying a conditioning medium for sperm cells to a conditioning chamber of a mesoscale device via an inlet of the conditioning chamber, the conditioning chamberplaced at an elevated position of the mesoscale device, relative to a control sample chamber of the mesoscale device,- applying a sperm sample comprising motile cells and non-motile cells from the selected one raw sperm sample of the selected one mammal to the control sample chamber via a sperm sample inlet of the control sample chamber, the control sample chamber placed at a lowered position of the mesoscale device, relative to the conditioning chamber of the mesoscale device,- the control sample chamber and the conditioning chamber being in fluid communication via pores in a cell permeable membrane, the cell permeable membrane having one surface facing the elevated position of the conditioning chamber and the cell permeable membrane having another surface facing the lowered position of the control sample chamber,- allowing motile cells in the sperm sample in the mesoscale device to move and migrate themselves from the lowered position of the control sample chamber, through the cell permeable membrane, to the elevated position of conditioning chamber during an incubation period for the motile cells to move, and- controlling at least one of the following parameters during the incubation period: a temperature inside the sample chamber, a temperature inside the conditioning chamber, a duration of the incubation period, and- where controlling at least one of the parameters during the incubation period is performed based upon parameters obtained from a sperm sample from the selected one raw sperm sample of the selected one mammal other than the sperm sample in the control sample chamber of the mesoscale device.

6. A mesoscale device comprising- at least one mesoscale device for establishing a probability of a sperm sample, from a selected one raw sperm sample of selected one mammal, being suitable for at least one of the following fertilisation methods: intrauterine insemination (IUI), in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI), and- at least one mesoscale device for increasing a probability of a sperm sample, from the selected one raw sperm sample of selected one mammal, being suitable for at least one of the following fertilisation methods: intrauterine insemination (IUI), in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI), and- where at least one of the following parameters of the mesoscale device is capable of being controlled based upon parameters obtained from the mesoscale device: a temperature inside of the sample chamber, a temperature inside the conditioning chamber, a duration of the incubation period, a temperature gradient during the incubation period.

7. A mesoscale device according to claim 6, where the mesoscale device comprises means for controlling the temperature of at least one of the sample chamber and the conditioning chamber, and where the means for controlling the temperature of at least one of the sample chamber and the conditioning chamber are controlled by parameters obtained from a raw sperm sample of a reference sample chamber of a mesoscale device.

8. A mesoscale device according to claim 6 or 7, where the mesoscale device comprises means for controlling the incubation period for the motile cells to move and migrate themselves from the sample chamber, through the cell permeable membrane, to the conditioning chamber, and where the means for controlling the incubation period are controlled by parameters obtained from a reference sample chamber of the mesoscale device.

9. Method for establishing a probability of a sperm sample, from a selected one raw sperm sample of selected one mammal, being suitable for at least one of the following fertilisation methods: intrauterine insemination (IUI), in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI), the sperm sample comprising motile cells and non-motile cells, the method comprising the steps of- applying one sperm sample comprising motile cells and non-motile cells from the selected one raw sperm sample of selected one mammal to a reference sample chamber of a mesoscale device via a sperm sample inlet of the reference sample chamber, the reference sample chamber being separate from possible other chambers of the mesoscale device and of possible other mesoscale devices,- applying another sperm sample comprising motile cells and non-motile cells from the selected one raw sperm sample of the selected one mammal to a control chamber of a mesoscale device via a sperm sample inlet of the control chamber, the control chamber being separate from possible other chambers of the mesoscale device or chambers of possible other mesoscale devices,- establishing at least one parameter of at least the motile cells, possibly also of the non- motile cells, in the reference sample chamber, comparing the at least one parameter established in the reference sample chamber with at least one parameter of at least the motile cells in the control chamber, possibly also of the non-motile cells, and selecting a fertilisation method and / or a fertilisation protocol based upon the comparison.

10. Method according to claim 9, where at least one parameter of at least the motile cells in the reference sample chamber is selected from the following parameters: anumber of motile cells, a number of progressive motile cells, a progressivity of the motile cells, a direction of movement of the motile cells, a speed of movement of the motile cells, a morphology of the motile cells.

11. A mesoscale device for establishing a probability of a sperm sample, from a selected one raw sperm sample of selected one mammal, being suitable for at least one of the following fertilisation methods: intrauterine insemination (IUI), in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI), the mesoscale device comprising- a reference sample chamber with a sperm sample inlet, the reference sample chamber being separate from possible other chambers of the mesoscale device including a control chamber,- a control chamber with a sperm sample inlet, the control chamber being separate from possible other chambers of the mesoscale device including the reference sample chamber,- the reference sample chamber and the control chamber being provided on the one and same mesoscale device, and each of the reference sample chamber and the separation chamber having a sperm sample inlet separate from each other, and- the control chamber comprising a control sample chamber and a conditioning chamber, the control sample chamber being provided with the sperm sample inlet of the control chamber, the sample chamber placed at a lowered position of the control chamber, relative to the conditioning chamber, and the conditioning chamber placed at an elevated position of the control chamber, relative to the control sample chamber,- the control sample chamber and the conditioning chamber being in fluid communication via pores in a cell permeable membrane, the cell permeable membrane having one surface facing the elevated position of the conditioning chamber and the cell permeable membrane having another surface facing the lowered position of the control sample chamber.

12. Use of a mesoscale device according to any of claims 6-8 for establishing a probability of a sperm sample, from a selected one raw sperm sample of selected one mammal, being suitable for at least one of the following fertilisation methods: Intrauterine insemination (IUI), in vitro fertilisation (IVF) or Intracytoplasmic sperm injection (ICSI).

13. Use of a mesoscale device according to claim 11 for increasing a probability of a sperm sample, from a selected one raw sperm sample of selected one mammal, being suitable for at least one of the following fertilisation methods: Intrauterine insemination (IUI), in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI).

Citation Information

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