Devices, systems, and methods for semen analysis

Abstract

Disclosed herein are devices, systems, and methods for analyzing one or more semen samples. Specifically disclosed is a device for analyzing one or more semen samples that may be a positive displacement device (e.g., a positive displacement pipette) that comprises a low-volume capillary. The device may require only a low volume of sample (e.g., about 10 µl) and the capillary may be transparent for electro-optical viewing and / or evaluation of motile sperm in the one or more semen samples. Additionally disclosed are methods for introducing the one or more semen samples into the device.

Description

Docket No. FMESM-P006-PCTDEVICES, SYSTEMS, AND METHODS FOR SEMEN ANALYSIS FIELD

[0001] The disclosure relates generally to devices, systems, and methods for analyzing one or more semen samples. In particular, embodiments of the disclosure include a positive displacement device that comprises a low-volume capillary, as well as methods for introducing the one or more semen samples into the device. Embodiments of the disclosure enable electro-optical viewing and / or evaluation of motile sperm in the one or more semen samples.BACKGROUND

[0002] Analysis of fluid samples, including semen samples, are generally labor-intensive and require the preparation and use of slides for viewing and / or evaluating the samples. Additionally, many sample analysis devices and systems are not disposable, resulting in inter-sample errors and increased labor and economic costs for washing and cleaning the devices and systems in-between the analysis of different samples.

[0003] Conventional sample analysis devices, systems, and methods are also prone to sampling and / or analysis error (e.g., dilution error) and / or biological contamination, making such conventional devices, systems, and methods unsuitable for use in general healthcare environments, such as physicians’ offices.

[0004] Given the foregoing, there exists a significant need for improved methods, devices, and systems for analyzing semen samples.Docket No. FMESM-P006-PCTSUMMARY

[0005] It is to be understood that both the following summary and the detailed description are exemplary and explanatory and are intended to provide further explanation of the invention as claimed. Neither the summary nor the description that follows is intended to define or limit the scope of the invention to the particular features mentioned in the summary or in the description.

[0006] In certain embodiments, the disclosed embodiments may include one or more of the features described herein.

[0007] Embodiments of the present disclosure are directed towards devices, systems, and methods for analyzing one or more semen samples, which provide one or more benefits over standard methods, devices, and systems used in the art. Non-limiting examples of such benefits include: (1) no need for the preparation or usage of slides for viewing and / or analysis of the sample, (2) a disposable tool (e.g., washing and handling not required after use), which saves both labor and inter-sample errors and effects, (3) eliminating biological contamination hazards, thereby enabling sample analysis in a variety of healthcare environments, including physicians’ offices, and (4) no dilution requirement, which also saves labor and eliminates a significant source of sampling and / or analysis error (e.g., dilution inaccuracy).

[0008] Some existing semen analysis machines evaluate sperm quality / motility by passing light through a semen sample. Such machines use a complementary semen analysis device to carry a semen sample, which is inserted into the machine for analysis of the sample and then can be removed and cleaned / re-used or discarded. Such semen analysis devices that carry the semen samples have a transparent area positioned such that, when the device is inserted into the machine, the transparent area lines up with a light source in the machine used to perform the evaluation. Prior art semen analysis devices such as those of U.S. Patents 8,460,942 and 7,252,642 may use a plunger to drawDocket No. FMESM-P006-PCTa semen sample into a tip of the device. The tip may contain a thin chamber with transparent upper and lower surfaces and be configured for insertion into a semen analysis machine.

[0009] A new semen analysis device in some embodiments does not require insertion into a sample for filling or use of a plunger but works with existing semen analysis machines. The new semen analysis device has a capillary motility chamber with internal volume, shape, and geometry to receive a semen sample from a filling point (alternatively called a filling port) via, e.g., a pipette, and spread the semen sample evenly throughout the capillary motility chamber by capillary forces. Some embodiments produce semen analysis results at least as accurate as prior art semen analysis devices using the same semen analysis machines. Loading the semen sample via a filling point with a sterile pipette aspirates the sample without contaminating it and avoids the introduction of bubbles. In some embodiments, the capillary motility chamber has the same thickness (e.g., 300 microns) and volume as prior art semen analysis devices at the point of testing (where the light source is positioned when the semen analysis device is inserted into the semen analysis machine), allowing for use with the existing machines and facilitating identical or better results as with the prior art devices.

[0010] At least one embodiment of the invention is a positive displacement device that comprises a low- volume capillary. In at least one example, the capillary may be transparent for electro-optical viewing and / or evaluation of motile sperm in the one or more semen samples. In at least one example, the positive displacement device is manufactured from one or more materials that are non-toxic to sperm. In at least one example, the device requires a low volume of sample (e.g., about 10 pl).

[0011] In at least one embodiment, the device for analyzing one or more semen samples comprises a filling point area, a filling point, a motility chamber, and a motility testing area. In at least oneDocket No. FMESM-P006-PCTexample, the filling point is used to introduce the one or more semen samples into the device. Further, the filling point is agnostic with respect to the specific type of laboratory tool or pipette, including being agnostic with respect to specific types of pipette tips, thereby enabling transfer and / or introduction of the sample quickly and efficiently into the motility chamber.

[0012] In at least one embodiment, the semen sample flows, by capillary action, into the motility chamber and the motility testing area. The sample, or at least a portion thereof, is drawn by capillary forces, into a capillary or tube, which is part of the motility testing area. The capillary or tube can be transparent for electro-optical viewing and / or evaluation of one or more aspects of the sperm sample (e.g., viewing and / or evaluation of motile sperm in the sperm sample).

[0013] In at least one embodiment, the motility chamber is configured to spread, using capillary forces, the sample evenly throughout the chamber and the motility testing area. In at least one example, the testing area can be used in conjunction with a semen analyzer device; for instance, the testing area may be disposed where a light emitting diode (LED) of a semen analyzer device is positioned when the positive displacement device is inserted into the semen analyzer device for sample analysis.

[0014] In at least one embodiment, the filling point may be generally round or circular, and may be tapered, with an outer diameter and an inner diameter. In at least one example, the inner diameter may be about 0.5 mm, the outer diameter may be about 1.50 mm, and the chamfer angle may be about 63-64 degrees (e.g., about 63.75 degrees). The chamfer angle is determined by the inner diameter, outer diameter, and depth of the filling point. In various embodiments, the chamfer angle may be between 50 and 75 degrees.Docket No. FMESM-P006-PCT

[0015] In at least one embodiment, the device comprises an internal channel, which may be generally rectangular in shape. The channel has an upper section and a lower section, both of which may be transparent.

[0016] In at least one embodiment, the channel comprises a capillary portion that enables evaluation of sperm motility as part of a motility testing area. In use, a light beam may be transmitted through the capillary portion, which contains at least a portion of the semen sample that has been introduced into the device. The sample portion can then be processed and / or analyzed (e.g., via an optical detector or photo-detector).

[0017] In at least one embodiment, the device may be manufactured in one continuous piece (e.g., by injection molding) and the motility testing chamber may be formed by inserting a metal piece into the device. This metal piece may have the same thickness and / or volume as that of the capillary portion or one or more parts thereof (e.g., about 0.3 mm thick).

[0018] At least one embodiment of the invention comprises one or more methods to introduce one or more semen samples into any of the devices described herein. In at least one example, a first method generally uses a pipette or other similar laboratory tool for transferring the sample into the device. In at least another example, a second method generally involves immersing a capillary tip or capillary portion of the device into the sample, thereby introducing the sample into the device.

[0019] Therefore, based on the foregoing and continuing description, the subject invention in its various embodiments may comprise one or more of the following features in any non-mutually-exclusive combination:• A device for analyzing a semen sample, the device comprising a chamber, a testing area adjacent to at least a portion of the chamber, and a filling point for intaking the semen sample, the filling point fluidly connected to the chamber;Docket No. FMESM-P006-PCTThe filling point comprises an opening configured to receive a pipette tip;The opening of the filling point having a greater diameter at a surface of the device than at a point below the surface of the device;The chamber being configured to spread the semen sample evenly throughout the chamber by capillary action;The filling point having a circular cross-section with a smallest diameter and a largest diameter;The smallest diameter being 0.5 millimeters;The largest diameter being 1.5 millimeters;A ratio of the largest diameter to the smallest diameter being 3:1;The smallest diameter of the filling point being smaller than a diameter of a tip of a smallest transfer device in a set of predetermined sample transfer devices;The largest diameter of the filing point being larger than a diameter of a tip of a largest transfer device of the set of predetermined sample transfer devices;The filling point having a chamfer;The chamfer having an angle of 50-75 degrees;The chamfer having an angle of 63.75 degrees;The filling point accommodating a plurality of different sizes of pipette tips; The device being injection molded in one piece;The chamber being formed by a metal piece inserted into the device and then removed to leave a void;The semen sample filling the chamber and the testing area by the capillary action;Docket No. FMESM-P006-PCTThe testing area being transparent on at least two opposite sides of the motility chamber such that one or more light beams can be transmitted through the testing area and the motility chamber;The filling point being positioned at a first end of the chamber;The device further comprising a second opening at a second end of the chamber; The filling point having a circular cross-section with a smallest diameter and a largest diameter;A ratio of an area of the filling point opening at the smallest diameter cross-section to an area of the chamber at the second opening is in a range of 1:6 to 1:7 to draw the semen sample into the chamber and spread it evenly throughout the chamber when the semen sample is placed in the filling point or the second opening;The aforementioned ratio being 1:6.8;The chamber having a thickness of 300 microns adjacent the testing area;The chamber having a maximum thickness of 360 microns at an end where the filling point is located;The chamber having a draft angle of 0.31 degrees;A device for analyzing a semen sample, the device comprising a filling point for intaking the semen sample, and one or more areas for analyzing the semen sample; The filling point having a chamfer and being fluidly connected to the one or more areas for analyzing the semen sample;The device being injection molded in one piece;The device further comprising a channel disposed in an interior of the device;Docket No. FMESM-P006-PCTA method for analyzing a semen sample, the method comprising transferring a semen sample into an analysis device, registering one or more optical density variations of sperm cells in the semen sample, thereby generating one or more registered optical density variations, translating the one or more registered optical density variations into electrical signals, routing the electrical signals to one or more electronic circuits, processing, by the one or more electronic circuits, the electrical signals, thereby generating processed electrical signals, and analyzing the processed electrical signals to calculate one or more parameters of the semen sample;The analysis device comprising a filling point comprising an opening configured to receive a pipette tip, and a motility chamber fluidly connected to the filling point; The opening having a greater diameter at a surface of the analysis device than at a point below the surface of the analysis device;The motility chamber being configured to spread the semen sample evenly throughout the chamber by capillary action;The transferring the semen sample further comprising introducing the semen sample into the filling point;The introducing the semen sample further comprising intaking 10 pl of the semen sample into a pipette, and ejecting the 10 pl of the semen sample into the filling point;The analysis device further comprising a tip fluidly connected to the motility chamber;Docket No. FMESM-P006-PCT• The transferring the semen sample comprising immersing the tip into the semen sample to fill the motility chamber by capillary action;• The filling point having a chamfer; and• The analysis device being injection molded in one piece.

[0020] These and further and other objects and features of the invention are apparent in the disclosure, which includes the above and ongoing written specification, as well as the drawings.BRIEF DESCRIPTION OF THE DRAWINGS

[0021] The accompanying drawings, which are incorporated herein and form a part of the specification, illustrate exemplary embodiments and, together with the description, further serve to enable a person skilled in the pertinent art to make and use these embodiments and others that will be apparent to those skilled in the art. The invention will be more particularly described in conjunction with the following drawings wherein:

[0022] FIG. 1 is a diagram of a device for analyzing one or more semen samples, according to at least one embodiment of the present disclosure.

[0023] FIGS. 2A-2D show various views of the device of FIG. 1, specifically a top view (FIG. 2A), a section view through line A-A of FIG. 2A (FIG. 2B), an end view of the device (FIG. 2C), and a side view of the device (FIG. 2D), according to at least one embodiment.

[0024] FIG. 3 shows various exemplary dimensions for portions of a device for analyzing one or more semen samples, according to at least one embodiment.

[0025] FIGS. 4A-4K show further details of portions of a device for analyzing one or more semen samples, specifically a top view of a first end of the device (FIG. 4A), a detail view of a filling point of the device (FIG. 4B), a section view through line G-G of FIG. 4A (FIG. 4C), a detail viewDocket No. FMESM-P006-PCTof area H of FIG. 4C (FIG. 4D), a side view of the first end of the device (FIG. 4E), a section view through line I-I of FIG. 4E (FIG. 4F), a bottom view of the first end of the device (FIG. 4G), a section view through line J-J of FIG. 4G (FIG. 4H), a detail view of area K of FIG. 4H showing a cross-sectional side view of a motility testing area of the device (FIG. 41), a top side perspective view of the device (FIG. 4J), and a detail view of area AC of FIG. 4J showing further details of the first end of the device (FIG. 4K), according to at least one embodiment.

[0026] FIGS. 5A-5B show various steps of a method of introducing a semen sample into one or more devices for analyzing semen samples, according to at least one embodiment of the present disclosure.

[0027] FIGS. 6A-6B show various steps of another method of introducing a semen sample into one or more devices for analyzing semen samples, according to at least one embodiment of the present disclosure.DETAILED DESCRIPTION

[0028] The present invention is more fully described below with reference to the accompanying figures.The following description is exemplary in that several embodiments are described (e.g., by use of the terms “preferably,” “for example,” or “in one embodiment”); however, such should not be viewed as limiting or as setting forth the only embodiments of the present invention, as the invention encompasses other embodiments not specifically recited in this description, including alternatives, modifications, and equivalents within the spirit and scope of the invention. Further, the use of the terms “invention,” “present invention,” “embodiment,” and similar terms throughout the description are used broadly and not intended to mean that the invention requires, or is limited to, any particular aspect being described or that such description is the only manner in which theDocket No. FMESM-P006-PCTinvention may be made or used. Additionally, the invention may be described in the context of specific applications; however, the invention may be used in a variety of applications not specifically described.

[0029] The embodiment(s) described, and references in the specification to “one embodiment”, “an embodiment”, “an example embodiment”, etc., indicate that the embodiment(s) described may include a particular feature, structure, or characteristic. Such phrases are not necessarily referring to the same embodiment. When a particular feature, structure, or characteristic is described in connection with an embodiment, persons skilled in the art may effect such feature, structure, or characteristic in connection with other embodiments whether or not explicitly described.

[0030] In the several figures, like reference numerals may be used for like elements having like functions even in different drawings. The embodiments described, and their detailed construction and elements, are merely provided to assist in a comprehensive understanding of the invention. Thus, it is apparent that the present invention can be carried out in a variety of ways, and does not require any of the specific features described herein. Also, well-known functions or constructions are not described in detail since they would obscure the invention with unnecessary detail. Any signal arrows in the drawings / figures should be considered only as exemplary, and not limiting, unless otherwise specifically noted. Further, the description is not to be taken in a limiting sense, but is made merely for the purpose of illustrating the general principles of the invention, since the scope of the invention is best defined by the appended claims.

[0031] It will be understood that, although the terms “first,” “second,” etc. may be used herein to describe various elements, these elements should not be limited by these terms. These terms are only used to distinguish one element from another. Purely as a non-limiting example, a first element could be termed a second element, and, similarly, a second element could be termed a first element,Docket No. FMESM-P006-PCTwithout departing from the scope of example embodiments. As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items. As used herein, the singular forms "a", "an," and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It should also be noted that, in some alternative implementations, the functions and / or acts noted may occur out of the order as represented in at least one of the several figures. Purely as a non-limiting example, two figures shown in succession may in fact be executed substantially concurrently or may sometimes be executed in the reverse order, depending upon the functionality and / or acts described or depicted.

[0032] It should also be noted that in some alternative implementations, the functions / acts noted may occur out of the order noted in the figures. For example, two figures shown in succession may in fact be executed substantially concurrently or may sometimes be executed in the reverse order, depending upon the functionality / acts involved.

[0033] As used herein, ranges are used herein in shorthand, so as to avoid having to list and describe each and every value within the range. Any appropriate value within the range can be selected, where appropriate, as the upper value, lower value, or the terminus of the range.

[0034] ‘ ‘About” means a referenced numeric indication plus or minus 10% of that referenced numeric indication. For example, the term “about 4” would include a range of 3.6 to 4.4. All numbers expressing quantities of ingredients, reaction conditions, and so forth used in the specification are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth herein are approximations that can vary depending upon the desired properties sought to be obtained. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of any claims, each numerical parameter should be construed in light of the number of significant digits and ordinaryDocket No. FMESM-P006-PCTrounding approaches.

[0035] The words “comprise,” “comprises,” and “comprising” are to be interpreted inclusively rather than exclusively. Likewise, the terms “include,” “including,” and “or” should all be construed to be inclusive, unless such a construction is clearly prohibited from the context. The terms “comprising” or “including” are intended to include embodiments encompassed by the terms “consisting essentially of’ and “consisting of.” Similarly, the term “consisting essentially of’ is intended to include embodiments encompassed by the term “consisting of.” Although having distinct meanings, the terms “comprising,” “having,” “containing,” and “consisting of’ may be replaced with one another throughout the description of the invention.

[0036] Conditional language, such as, among others, “can,” “could,” “might,” or “may,” unless specifically stated otherwise, or otherwise understood within the context as used, is generally intended to convey that certain embodiments include, while other embodiments do not include, certain features, elements and / or steps. Thus, such conditional language is not generally intended to imply that features, elements and / or steps are in any way required for one or more embodiments or that one or more embodiments necessarily include logic for deciding, with or without user input or prompting, whether these features, elements and / or steps are included or are to be performed in any particular embodiment.

[0037] Wherever the phrase “for example,” “such as,” “including” and the like are used herein, the phrase “and without limitation” is understood to follow unless explicitly stated otherwise.

[0038] “Typically” or “optionally” means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where said event or circumstance occurs and instances where it does not.

[0039] Some embodiments of novel devices, systems, and methods for analyzing one or more samples,Docket No. FMESM-P006-PCTincluding one or more semen samples, have at least the following properties: (1) virtual positive displacement, such that low volume (e.g., about 10 pl) samples can be analyzed, (2) a precise, thin, rectangular, and / or transparent capillary for electro-optical viewing and / or evaluation of motile sperm concentration (MSC) in the sample, and (3) a convenient, easy-to-use form factor, non-toxic materials, and a design that provides safety from biological hazards, such that sample analysis can be performed in a variety of medical and / or healthcare environments, including physician’s offices.

[0040] In at least one embodiment, a device (e.g., a tool such as, for instance, a pipette or any other device that can intake and eject a sample) is disclosed for analyzing one or more semen samples. The device may, in at least one example, be disposable and / or made from disposable materials. The materials may further be non-toxic to semen and / or one or more biological compounds or cells contained therein (e.g., sperm cells). The materials may, in at least one example, be generally non- hazardous, including, for instance, biologically non-hazardous. Therefore, at least one embodiment does not require special storage and / or handling, and is suitable for use in physicians’ offices, medical offices, and other healthcare environments.

[0041] In at least one embodiment, a device for analyzing one or more semen samples is a virtual positive displacement device (e.g., virtual positive displacement pipette). In at least one example, the positive displacement device can sample low volumes (e.g., about 10 pl of sample).

[0042] In at least one embodiment, a device for analyzing one or more semen samples comprises a capillary or other tube that is disposed at least partially within one or more internal spaces and / or regions of the device. In at least one example, the capillary or tube may be sufficiently thin and / or transparent to enable precise electro-optical viewing and / or evaluation of motile sperm cells (“MSC”). The capillary or tube may be any suitable cross-sectional shape, including, for instance,Docket No. FMESM-P006-PCTrectangular, circular, polygonal, or the like.

[0043] In at least one embodiment, the device for analyzing one or more semen samples is manufactured in one continuous piece (e.g., by injection molding).

[0044] In at least one embodiment, the device for analyzing one or more semen samples is manufactured from one or more materials that are non-toxic to sperm. Non-limiting examples of such materials include one or more plastics, one or more polymers, and the like, such as, for instance, one or more synthetic polymers (e.g., polystyrene PG79). Toxicity of the device, at least in relation to sperm cells, can be determined by sperm motility decay in comparison with a standard control (e.g., crystalline glass capillaries). By that measure, Polystyrene PG79 is very sperm compatible.

[0045] Turning now to FIG. 1, a device 100 is shown for analyzing one or more semen samples. Specific exemplary dimensions of the device, and various portions thereof, will be discussed further below herein. Generally, the device 100 comprises a first end 102 disposed opposite to a second end 104. Both the first end 102 and the second end 104 are connected to a body 106, which is disposed between the first end 102 and the second end 104. The body 106 further comprises a rib 116 that protrudes above a horizontal surface of the body 106. The rib 116 functions for guiding the device into a machine (e.g., a semen analyzer device as described further below herein) and to ensure that the device 100 is fully and correctly inserted into the machine. In use, a sample (e.g., a semen sample) is introduced into the first end 102, and then proceeds into a capillary or tube. The sample may be a low volume sample (e.g., about 10 pl of semen sample).

[0046] Specifically, the first end 102 comprises a filling point area 108, a filling point 110, a motility chamber 112, a motility testing area 114, and feature 115. The filling point area 108 may generally be disposed around at least a portion of the circumference of the filling point 110. The filling point may generally be round or circular in shape, and is used to introduce a sample (not shown) intoDocket No. FMESM-P006-PCTthe device 100. The filling point 110 is agnostic with respect to the specific type of laboratory tool or pipette, including being agnostic with respect to specific types of pipette tips, thereby enabling transfer and / or introduction of the sample quickly and efficiently into the motility chamber 112. The feature 115 is used for interaction with an analysis machine, such as a semen analyzer, and specifically serves as a stopper to ensure the capillary reaches the correct position for reading / analyzing the semen sample.

[0047] Methods of introducing such sample will be discussed further below herein, but include, as nonlimiting examples, a first method of using a pipette or other similar laboratory tool for transferring samples, and a second method of immersing a capillary tip in the sample.

[0048] Regardless of the method of introduction of the sample, the sample flows, by capillary action, into the motility chamber 112 and the motility testing area 114. The sample, or at least a portion thereof, is drawn by capillary forces into a capillary or tube, which is part of motility testing area 114, as described in further detail below herein. The capillary or tube can be transparent for electro-optical viewing and / or evaluation of one or more aspects of the sperm sample (e.g., viewing and / or evaluation of motile sperm in the sperm sample).

[0049] The motility chamber 112 is configured to spread the sample evenly throughout the chamber 112 and the testing area 114 using capillary forces. The thinness of the chamber 112 relative to its width causes capillary forces to be exerted on the sample and spread it evenly throughout the chamber. The ratio between the inner diameter (and hence, inner area) of the filling point and the area of the outlet at the end of the capillary chamber is important for ensuring smooth, complete, and uniform sample entry into and throughout the motility chamber. In some embodiments of the present invention, for example as depicted in the figures, the ratio between the inner diameter of the filling point and the area of the outlet at the end of the capillary chamber is preferably betweenDocket No. FMESM-P006-PCT1:6 and 1:7, and more preferably 1:6.8.

[0050] Additionally, the ratio between the outer and inner diameters of the filling point is important to facilitate proper sample flow into the capillary chamber while ensuring full compatibility with different types of pipette tips used in various laboratories. In particular, it is preferable that the inner diameter of the filling point is smaller than the diameter of the tip of a predetermined pipette (or other sample transfer device), or the diameter of the tip of the smallest of a set of predetermined pipettes (or other sample transfer devices), and that the outer diameter of the filing point is larger than the diameter of the tip of a predetermined pipette (or other sample transfer device), or the diameter of the tip of the largest of a set of predetermined pipettes (or other sample transfer devices). If the inner diameter is larger than the pipette tip diameter, the pipette tip may enter the chamber hole which may cause filling issues. If the outer diameter is smaller than the pipette tip diameter, the pipette will not be able to fit into the filling point, and some of the sample may spill onto the surface of the device for analyzing a semen sample, and there may be insufficient sample received within the chamber, such that the chamber is not filled evenly and analysis may suffer. Further, that may cause an issue with contamination and lack of hygiene. Furthermore, the inner diameter may preferably be as large as possible while satisfying that preference of being smaller than the pipette tip, in order to allow rapid filing of the chamber and avoid backflow. The outer diameter may preferably be as small as possible while satisfying that preference of being larger than the pipette tip, in order to take up as little space as possible on the device for semen analysis, backflow Thus, the ratio of inner to outer diameter of the filing port may preferably be selected based on the intended pipette or other filling device, or set of intended filling devices, to achieve those preferred outcomes. In some embodiments of the present invention, for example as depicted in the figures, the ratio between the outer and inner diameters of the filling point is preferably 3:1.Docket No. FMESM-P006-PCT

[0051] In at least one example, the chamber 112 has a roughly polygonal (e.g., rectangular) cross-sectional shape. The chamber 112 may further have a small draft angle (e.g., about 0.31 degrees) that enables, e.g., ease of production of the chamber 112 and / or other portions of the device. The testing area 114 can be used in conjunction with a semen analyzer device; for instance, the testing area 114 may be disposed where a light emitting diode (LED) of a semen analyzer device is positioned when the device 100 is inserted in the semen analyzer device. Thus, in at least one example, the device 100 can be inserted into such a semen analyzer such that the LED is positioned in or near the testing area 114. The polygonal (e.g., rectangular) cross-sectional shape of the chamber 112 can (1) provide convenient and accurate reading of the semen sample inside the semen analyzer, (2) provide ease of production advantages, and (3) accommodate a sample size of about 10 pl which, in at least one example and as described further below herein, is a preferable sample size for transferring to the device 100 and reading from the device 100.

[0052] FIG. 2A shows a top view of the device 100 shown in FIG. 1. As in FIG. 1, FIG. 2A shows the first end 102 (with the filling point area 108, the filling point 110, the motility chamber 112, and the motility testing area 114), the second end 104, and the body 106 (with the rib 116). Taking a section through line A- A results in FIG. 2B.

[0053] FIG. 2C shows an end view of the device 100 shown in FIG. 1, taken from the first end 102. The motility chamber 112 and the motility testing area 114 are shown. The filling area 108, as well as the rib 116, which are both raised vertically above a horizontal plane of the device 100, are also shown.

[0054] FIG. 2D shows a side view of the device 100 shown in FIG. 1, the other side view being a mirror image thereof. From the side view, the filling point 110 is not seen due to the raised elevation of the filling point area 108.Docket No. FMESM-P006-PCT

[0055] Turning now to FIG. 3, some exemplary dimensions for portions of the device 100 are shown.Specifically, distance di, which represents an overall length of device 100, may be about 130 millimeters (mm). Distance d2, which represents a length of the second end 104 only, may be about 41-42 mm (e.g., about 41.65 mm). Distance ds, which represents a width of the second end 104, may be about 25-26 mm (e.g., about 25.50 mm). As can be seen, the second end 104 may be wider than both the first end 102 and the body 106. This second end 104 may be conveniently sized for a person to hold the device 100 by when transporting it. Distance d4, which represents the width of the body 106 (as well as a portion of the first end 102 that is connected to, and / or closer to, the body 106), may be about 12 mm.

[0056] Further details of portions of the device 100, as well as exemplary dimensions thereof, are shown in FIGS. 4A-4I. FIG. 4A shows a top view of the first end 102 of the device 100. Specifically shown are the filling point area 108, the filling point 110, the motility chamber 112, and the motility testing area 114.

[0057] Distance ds, which represents a width of the filling point area 108, may be about 7.20 mm.Accordingly, distance de, which represents half of the aforementioned width (that is, from one side of the filling point area 108 to an imaginary center line drawn through the filling point area, which corresponds with section line G-G), may be about 3.60 mm. Distance d?, which represents a length (that is, a measurement along an imaginary line parallel to section line G-G) of the filling point area 108, may be about 3.50 mm. Distance ds, which represents a portion of the aforementioned length of the filling point area 108, may be about 0.90 mm. Distance d<_>, which represents a distance from an end point of the first end 102 to the filling point 108, may be about 9.2-9.3 mm (e.g., about 9.24 mm).

[0058] In at least one embodiment, and as shown in FIG. 4A, the filling point 110 may have two differentDocket No. FMESM-P006-PCTdiameters, e.g. at the top (closest to the surface) and bottom: an outer or largest diameter and an inner or smallest diameter. Further details on the filling point 110 are provided below herein (e.g., with respect to FIG. 4B). Radius n, which represents a radius between the center of the filling point and an inner edge of the filling point area 108, may be about 1.20 mm.

[0059] With respect to the motility chamber 112, the total width of the chamber (not shown) is about 3.70 mm. The total length of the chamber is represented by distance ds plus distance d<_> plus radius n. Additionally, distance dio, which represents a width of the motility testing area 114, which can be a transparent area through which a semen sample in the chamber can be read and / or analyzed,, may be about 2.7-2.8 mm (e.g., about 2.73 mm). Distance du, which represents a length (that is, a measurement along an imaginary line parallel to section line G-G) of the motility testing area 114, may be about 7.5-7.6 mm (e.g., about 7.55 mm). Distance di2, which represents a distance from an end point of the first end 102 to the motility chamber 112, may be about 1.70 mm.

[0060] Distance di3, which represents the narrowest width of the first end 102, may be about 4.7-4.9 mm (e.g., about 4.80) mm. Distance du, which represents a portion of the length of the first end 102, may be about 16.0-16.1 mm (e.g., about 16.04 mm).

[0061] FIG. 4B shows the filling point 110 and a section taken through line A-A. Exemplary dimensions of the inner diameter 111 may be about 0.5 mm, the outer diameter 113 may be about 1.50 mm, and the chamfer angle a2 may be about 63-64 degrees (e.g., about 63.75 degrees). In at least one example, a ratio of the outer diameter to the inner diameter is about 3:1. Channel 118 is also shown, which will be described further below herein.

[0062] Taking a section through line G-G in FIG. 4A results in FIG. 4C, which shows, inter alia, internal channel 118. The channel is generally rectangular in cross-section. The filling point 110 and the motility chamber 112 are fluidly connected. The motility testing area 114 (not shown in this figure)Docket No. FMESM-P006-PCTis transparent and serves as a window to the motility chamber so that optical semen analysis can occur.

[0063] Distance dis, which represents a maximum thickness of the channel, may be about 0.36 mm ±0.025 mm, or 360 micron ± 25 micron. The minimum thickness of the channel (not shown) may be about 0.30 mm or 300 microns at the proximal end, near the filling point. Angle a4, which represents a draft angle of the channel, may be about 0.31 degrees. The thickness of the channel may vary gradually and linearly along the chamber from the minimum thickness near the filling point to the maximum thickness at the distal opposite end where there is a second opening, due to the aforementioned draft angle. Distance dn, which represents a distance between the channel and a surface (e.g., an upper surface and / or lower surface) of the first end 102, may be about 0.37 mm. Distance dis is the inner diameter of the filling point 110 and may be about 0.50 mm.

[0064] Upper section 120 is material that is disposed above (that is, closer to the upper surface of the first end 102) the channel, and lower section 122 is material that is disposed below (that is, closer to the lower surface of the first end 102) the channel. The upper section 120 and / or the lower section 122 may be transparent.

[0065] In use, a light beam may be transmitted through the channel 118 from above, which contains at least a portion of a sample (e.g., a semen sample) that has been introduced into the device 100 and has been spread evenly throughout motility testing chamber 112 and motility testing area 114. An optical detector (not shown), which may be disposed below channel 118, and exterior to the device 100, registers optical density variations caused by moving sperm cells. Such optical density variations may then be translated into electrical signals by the optical detector or photo-detector. The signals may then be routed to one or more electronic circuits (not shown) to be filtered, digitized, and processed to indicate motile sperm concentration (MSC). Thus, the channel 118 mayDocket No. FMESM-P006-PCTbe used for electro-optical viewing and evaluation of motile sperm in the sample. The aforementioned optical detector or photo-detector, electronic circuits, and filtering, digitization, and / or processing methods, are all known in the art.

[0066] As described above herein, the device 100 may be manufactured in one continuous piece (e.g., by injection molding) and the motility testing chamber 112 may be formed by inserting a metal piece into the device 100. This metal piece may have the same thickness and / or volume as that of the channel 118 or one or more parts thereof. A non-limiting example of such thickness is about 0.3 mm.

[0067] Additional angles of various aspects of the device 100 are also shown. Specifically, angle ai may be about 10 degrees and angle a2 (the chamfer angle of the filling point 110) may be about 63.75 degrees. Angle ai provides for easier manufacturing (e.g., by injection molding). Angle a2 is an optimum angle at which, in at least one example, smooth and effective filling can be obtained with a plurality of pipettes having a range of different pipette tip diameters.

[0068] Taking a detail view of area H results in FIG. 4D, which shows a portion 124 of channel 118 adjacent the filling point. Radius r2, which represents a radius of curvature of the rear of portion 124, may be about 0.14-0.16 mm (e.g., about 0.15 mm). Chamfer angle a2 is also shown.

[0069] FIG. 4E is a side view of the first end 102. Taking a section through line I-I results in FIG. 4F, which shows an interior of the first end 102. Specifically shown is the channel 118. Distance di9, which represents a length of the channel, may be about 9-12 mm (e.g., about 10.95 mm). Radius ra, which represents a radius of curvature of the end of channel 118 in this view, may be about 1.70 mm.

[0070] FIG. 4G shows a bottom view of the first end 102. In this view, the filling point area 108 and the filling point 110 are not visible. Angle as, which represents an angle of a narrowest point of theDocket No. FMESM-P006-PCTfirst end 102 that is nearest to the motility chamber 112, may be about 60 degrees. Distance d2o, which represents a widest width of the first end 102, may be about 12.00 mm. Distance d2i, which represents a distance between an outer edge of motility testing area 114 and an outer arc of feature 126, may be about 1.80 mm. Feature 126 assists in creating or generating the motility chamber during manufacturing (e.g., an injection molding process). Radius r4, which represents a radius of the generally hemispherical feature 126, may be about 1.7-1.8 mm (e.g., about 1.75 mm). Distance d22, which represents a width of feature 115, may be about 9.20 mm. Accordingly, distance d23, which represents half of the aforementioned width of feature 115, may be about 4.60 mm. Distance d24, which represents a length of feature 115, may be about 2.50 mm.

[0071] Taking a section through line J-J results in FIG. 4H. Distance d25, which represents a width of the channel 118, may be about 3.60-3.80 mm (e.g., about 3.70 mm).

[0072] Taking a detail view of area K results in FIG. 41, which shows a cross-sectional side view of the channel 118. Radius r.5, which represents a radius of curvature of the side of channel 118, may be about 0.15 mm.

[0073] FIG. 4J shows a top side perspective view of the device 100, with the first end 102 disposed opposite the second end 104, the body 106 disposed between the first end 102 and the second end 104, and the rib 116 on the body 106. Also shown are filling point area 108, a filling point 110, a motility chamber 112, a motility testing area 114, and feature 115, all of which have been described above herein. Taking a detail view of first end 102, marked by area AC, results in FIG. 4K. In FIGS. 4K and 4J, the entire top surface of the device 100 has been rendered transparent for ease of viewing internal aspects of the device such as the motility chamber 112.

[0074] FIG. 4K shows, in greater detail, filling point area 108, a filling point 110, a motility chamber 112, a motility testing area 114, and feature 115. Motility chamber 112 is shaded for ease of viewing.Docket No. FMESM-P006-PCT

[0075] As described above herein, one or more methods may be used to introduce a sample (e.g., a semen sample) into any of the devices described herein. Generally, a first method uses a pipette or other similar laboratory tool for transferring the sample into the device for analyzing one or more semen samples, and a second method involves immersing a capillary tip in the sample.

[0076] Turning now to FIG. 5A, a method 500 is shown of introducing a semen sample into any of the devices for semen analysis described herein and testing the semen sample using the device. First, at block 502, a semen sample is transferred (e.g., via a pipette, such as a laboratory sterile pipette, or any similar laboratory tool for transferring fluid samples) to a filling point of the device (e.g., filling point 110). At block 504, the transferred semen sample fills a motility chamber of the device (e.g., motility chamber 112). The semen sample also fills a motility testing area of the device (e.g., motility testing area 114), as shown at block 506. The filling of both the motility chamber and the motility testing area occurs by capillary action, as well as the force of the pipette or other similar laboratory tool pushing the sample into the filling point. At block 508, optical density variations in the sperm cells of the semen sample are registered (e.g., by an optical detector, after insertion of the device for semen analysis into a semen analyzing apparatus). At block 510, the registered optical density variations are translated into electrical signals (e.g., by the optical detector). At block 512, the electrical signals are routed to one or more electronic circuits for processing. Such processing may include, for instance, filtering and / or digitizing the electrical signals. Finally, at block 514, the processed signals are analyzed to calculate one or more parameters of the semen sample (e.g., MSC of the semen sample).

[0077] In at least one example, shown in FIG. 5B, block 502 further comprises (1) intaking 10 pl of the sample into the pipette or laboratory tool, as shown at block 516, and (2) ejecting the 10 pl of the sample from the pipette or laboratory tool into the filling point 110, as shown at block 518. In thisDocket No. FMESM-P006-PCTembodiment, 10 pl is the exact amount required for filling the device being used (e.g., device 100), based on the dimensions of the filling point and motility chamber. In other embodiments using differently sized devices, for example for different analysis machines, the volume used may be different. Users can set a pipette or other filling device to intake and / or eject 10 pl of the semen sample, thus ensuring the motility chamber, and particularly the portion of the chamber below the motility testing area, is filled by the sample, without the sample spilling out of the motility chamber (e.g., out of the open distal end or filling point). The tip of the pipette or laboratory tool may be, for instance, smaller than about 1.13 mm, thereby ensuring controlled and accurate filling of the filling point 110.

[0078] FIG. 6A shows an alternative or additional method 600 to method 500 of introducing a semen sample into any of the devices for analyzing semen samples described herein. First, at block 602, a semen sample is transferred (e.g., via immersing a capillary tip) to a filling point of the device through an opening on the end of the device, at the end of motility chamber 112. The capillary tip may be, for instance, the tip of the device 100 with the capillary portion 124). Thus, by directly immersing a tip of the device 100 into a semen sample, the sample (or a portion thereof) is transferred into the device by capillary forces. At block 604, the transferred semen sample fills a motility chamber of the device (e.g., motility chamber 112). The semen sample also fills a motility testing area of the device (e.g., motility testing area 114), as shown at block 606. The filling of both the motility chamber and the motility testing area occurs by capillary action. At block 608, optical density variations in the sperm cells of the semen sample are registered (e.g., by an optical detector). At block 610, the registered optical density variations are translated into electrical signals (e.g., by the optical detector). At block 612, the electrical signals are routed to one or more electronic circuits for processing. Such processing may include, for instance, filtering and / orDocket No. FMESM-P006-PCTdigitizing the electrical signals. Finally, at block 614, the processed signals are analyzed to calculate one or more parameters of the semen sample (e.g., MSC of the semen sample).

[0079] In at least one example, shown in FIG. 6B, block 602 further comprises, at block 616, dipping a portion of the semen analysis device (e.g., the portion nearest the motility chamber 112) about 5 mm into the sample at an inclination angle of about 45 degrees. This results in a portion of the semen sample being introduced, by capillary forces, into the motility chamber 112.

[0080] In at least one embodiment, a method for analyzing a semen sample comprises transferring a semen sample into an analysis device (e.g., any of the devices described herein), registering one or more optical density variations of sperm cells in the semen sample, thereby generating one or more registered optical density variations, translating the one or more registered optical density variations into electrical signals, routing the electrical signals to one or more electronic circuits, processing, by the one or more electronic circuits, the electrical signals, thereby generating processed electrical signals, and analyzing the processed electrical signals to calculate one or more parameters of the semen sample. The analysis device may, in at least one example, comprise a filling point comprising an opening configured to receive a pipette tip, where the opening has a greater diameter at a surface of the analysis device than at a point below the surface of the analysis device, and a motility chamber fluidly connected to the filling point, where the motility chamber is configured to spread the semen sample evenly throughout the chamber by capillary action.

[0081] The aforementioned transferring the semen sample may further comprise introducing the semen sample into the filling point.

[0082] The introducing the semen sample may further comprise intaking 10 pl of the semen sample into a pipette, and ejecting the 10 pl of the semen sample into the filling point.

[0083] In at least one example, the analysis device may further comprise a tip fluidly connected to theDocket No. FMESM-P006-PCTmotility chamber. Additionally, the transferring the semen sample may comprise immersing the tip into the semen sample to fill the motility chamber by capillary action.

[0084] In at least one example, the aforementioned filing point may comprise a chamfer.

[0085] In at least one example, the analysis device is injection molded in one piece.

[0086] Regardless of which of the aforementioned methods (including, but not limited to, methods 500 and / or 600) are used, (1) the motility chamber spreads the introduced semen sample evenly throughout the chamber and / or the motility testing area using capillary forces, and (2) the introduced sample can be viewed, evaluated, and / or analyzed electro-optically (e.g., by an optical detector or photo-detector).

[0087] Thus, embodiments of the invention disclosed herein have various advantages over existing sampling, analysis, and test-chamber devices, systems, and methods. Such advantages include, for instance, (1) no need for the preparation or usage of slides for viewing and / or analysis of the sample, (2) a disposable tool (e.g., washing and handling not required after use), which saves both labor and inter-sample errors and effects, (3) eliminating biological contamination hazards, thereby enabling sample analysis in a variety of healthcare environments, including physicians’ offices, and (4) no dilution requirement, which also saves labor and eliminates a significant source of sampling and / or analysis error (e.g., dilution inaccuracy).

[0088] These and other objectives and features of the invention are apparent in the disclosure, which includes the above and ongoing written specification.

[0089] The foregoing description details certain embodiments of the invention. It will be appreciated, however, that no matter how detailed the foregoing appears in text, the invention can be practiced in many ways. As is also stated above, it should be noted that the use of particular terminology when describing certain features or aspects of the invention should not be taken to imply that theDocket No. FMESM-P006-PCTterminology is being re-defined herein to be restricted to including any specific characteristics of the features or aspects of the invention with which that terminology is associated.

[0090] The invention is not limited to the particular embodiments illustrated in the drawings and described above in detail. Those skilled in the art will recognize that other arrangements could be devised. The invention encompasses every possible combination of the various features of each embodiment disclosed. One or more of the elements described herein with respect to various embodiments can be implemented in a more separated or integrated manner than explicitly described, or even removed or rendered as inoperable in certain cases, as is useful in accordance with a particular application. While the invention has been described with reference to specific illustrative embodiments, modifications and variations of the invention may be constructed without departing from the spirit and scope of the invention as set forth in the following claims.

Claims

1. Docket No. FMESM-P006-PCTWhat is claimed is:

1. A device for analyzing a semen sample, comprising:a chamber;a testing area adjacent to at least a portion of the chamber; anda filling point for intaking the semen sample, the filling point fluidly connected to the chamber,wherein the filling point comprises an opening configured to receive a pipette tip, wherein the opening has a greater diameter at a surface of the device than at a point below the surface of the device,wherein the chamber is configured to spread the semen sample evenly throughout the chamber by capillary action.

2. The device of claim 1 , wherein the filling point has a circular cross-section with a smallest diameter and a largest diameter.

3. The device of claim 2, wherein the smallest diameter is 0.5 millimeters, and wherein the largest diameter is 1.5 millimeters.

4. The device of claim 2, wherein a ratio of the largest diameter to the smallest diameter is 3 : 1.

5. The device of claim 2, wherein the smallest diameter of the filling point is smaller than a diameter of a tip of a smallest transfer device in a set of predetermined sample transfer devices, and the largest diameter of the filing point is larger than a diameter of a tip of a largest transfer device of the set of predetermined sample transfer devices.

6. The device of claim 1 , wherein the filling point has a chamfer.

7. The device of claim 6, wherein the chamfer has an angle of 50-75 degrees.Docket No. FMESM-P006-PCT8. The device of claim 1, wherein the filling point accommodates a plurality of different sizes of pipette tips.

9. The device of claim 1, wherein the device is injection molded in one piece, and wherein the chamber is formed by a metal piece inserted into the device and then removed to leave a void.

10. The device of claim 1, wherein the semen sample fills the chamber and the testing area by the capillary action.

11. The device of claim 1 , wherein the testing area is transparent on at least two opposite sides of the motility chamber such that one or more light beams can be transmitted through the testing area and the motility chamber.

12. The device of claim 1, wherein the filling point is positioned at a first end of the chamber, further comprising a second opening at a second end of the chamber.

13. The device of claim 12, wherein the filling point has a circular cross-section with a smallest diameter and a largest diameter, and wherein a ratio of an area of the filling point opening at the smallest diameter cross-section to an area of the chamber at the second opening is in a range of 1:6 to 1:7 to draw the semen sample into the chamber and spread it evenly throughout the chamber when the semen sample is placed in the filling point or the second opening.

14. The device of claim 13, wherein the ratio is 1:6.8.

15. The device of claim 1, wherein the chamber has a thickness of 300 microns adjacent the testing area.

16. The device of claim 15, wherein the chamber has a maximum thickness of 360 microns at an end where the filling point is located.Docket No. FMESM-P006-PCT17. The device of claim 16, wherein the chamber has a draft angle of 0.31 degrees.

18. A device for analyzing a semen sample, comprising:a filling point for intaking the semen sample; andone or more areas for analyzing the semen sample,wherein the filling point has a chamfer and is fluidly connected to the one or more areas for analyzing the semen sample.

19. The device of claim 18, wherein the device is injection molded in one piece.

20. The device of claim 18, further comprising a channel disposed in an interior of the device.

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