Evaporation limiting inserts for reagent containers and related usage methods

Abstract

An insert for a liquid holding container may include a body comprising a wall, a first open end and a second open end, and an inner cavity extending from the first open end to the second open end. The insert may also include a plurality of first openings formed in the wall between the first and second ends, each of the first openings defining an area, and one or more second openings formed in the wall between the first and second ends, each of the one or more second openings defining an area larger than that defined by any of the first openings, wherein at least one of the one or more second openings is located closer to the first end than any of the first openings, and wherein the dimensions of each of the first and second openings are adapted to allow liquid to pass through.

Description

[0001] This application is a divisional application of the patent application filed on March 2, 2018, with application number 201880015707.6 and title "Evaporation limiting insert for reagent container and related usage method".

[0002] Cross-reference of related applications

[0003] This patent application claims the benefit of U.S. Provisional Patent Application No. 62 / 466,856, filed March 3, 2017, pursuant to 35 U.SC §119, the entire contents of which are incorporated herein by reference. Technical Field

[0004] This disclosure relates to evaporation-limiting inserts for reagent containers and related methods of use. Background Technology

[0005] Automated analytical procedures used to determine the presence of an analyte in a sample typically require the use, handling, and / or manipulation of liquid solutions and / or suspensions. Such liquid solutions and / or suspensions are often stored on the analytical instrument in a container accessible by a pipetting device (e.g., a robotic pipette). The contents of the container can be accessed during instrument operation through the open end of the container (e.g., unsealed and exposed to the atmosphere), but it may be necessary to access the contents through permeable seals, filters, and / or diaphragms. However, leaving the container open results in the evaporation of some portion of the liquid contents, potentially leading to an increase in the concentration of at least one component of the liquid solution or suspension. Furthermore, liquid solutions or suspensions may need to be mixed to retain the solute in the solution or the material, such as solid or semi-solid particles, in the suspension. The process of mixing liquid solutions or suspensions can increase the evaporation rate of the mixture.

[0006] Hollow inserts that limit the surface area of ​​a liquid exposed to the atmosphere can be placed inside a container to restrict evaporation. These inserts may include openings arranged to facilitate mixing of liquid solutions or suspensions. However, one possible consequence of mixing is the formation of a film over the opening above the liquid level, which can lead to a vacuum within the container. Detergent-based liquids are particularly prone to forming such films. The surface tension of the film may be high enough that the level difference between the inside and outside of the insert does not produce a pressure differential that would damage the film. This level difference can result in inaccurate level sensing, causing the instrument to sense more or less liquid solution or suspension than actually exists in the container. Summary of the Invention

[0007] On one hand, the present invention relates to an insert for a liquid holding container, the insert comprising a body including a wall, a top end and a bottom end of an opening, and a generally tubular inner cavity extending from the top end of the opening to the bottom end of the opening; a plurality of first openings formed in the wall between the top end and the bottom end, each first opening defining an area; and one or more second openings formed in the wall between the top end and the bottom end, each of the one or more second openings defining an area larger than the area defined by any first opening, wherein at least one of the one or more second openings is located closer to the top end than any first opening, and wherein the dimensions of each of the first openings and the second openings are adapted to allow liquid to pass through.

[0008] The thickness of the wall immediately surrounding each of the first openings is greater than the thickness of the wall immediately adjacent to each of the one or more second openings. The thickness of the wall immediately surrounding each of the first openings is approximately 0.5 mm to approximately 1.5 mm. The thickness of the wall immediately surrounding each of the one or more second openings is approximately 0.10 mm to approximately 0.40 mm. The thickness of the wall immediately surrounding each of the first openings is approximately 1.0 mm, and the thickness of the wall immediately surrounding each of the one or more second openings is approximately 0.25 mm. The wall includes a chamfer around each of the one or more second openings. The chamfer is a four-sided chamfer. Each of the one or more second openings is collinear with at least two of the first openings. Each of the one or more second openings is rectangular or square in shape. The width of each of the one or more second openings is approximately 2.0 mm to approximately 8.0 mm, approximately 2.0 mm to approximately 7.0 mm, approximately 2.0 mm to approximately 6.0 mm, approximately 3.0 mm to approximately 5.0 mm, approximately 4.0 mm, or approximately 3.8 mm. The width of each of the one or more second openings is at least approximately 2.0 mm. Each of the first openings is circular in shape. The diameter of each of the one or more first openings is approximately 1.0 mm to approximately 4.0 mm, approximately 1.0 mm to approximately 3.0 mm, or approximately 2.0 mm. The diameter of each of the one or more first openings is at least approximately 1.0 mm. The ratio of the area of ​​any of the one or more second openings to the area of ​​any of the first openings is at least approximately 2.0. The ratio of the area of ​​any of the one or more second openings to the area of ​​any of the first openings is approximately 2.0 to approximately 8.0, approximately 3.0 to approximately 6.0, approximately 3.5 to approximately 5.0, approximately 4.5 to approximately 4.6, or approximately 4.0. The pressure required to remove a liquid film spanning any of the one or more second openings is less than the pressure required to remove a liquid film spanning any of the first openings. The body tapers radially inward from the top to the bottom. The inner diameter of the body is larger at the top than at the bottom. At least one first opening is located below the midpoint of the body length. Most of the first openings are located below the midpoint of the body length. Two-thirds or more of the first opening is located below the midpoint of the body length. Each of one or more second openings is located above the midpoint of the body length. The insert includes at least one groove in a wall extending from the bottom end of the insert toward the top end. The at least one groove includes two opposing grooves, each extending from the bottom end toward the top end. The at least one groove is a recess in the bottom end of the insert. The body further includes two or more resilient tabs at the top end of the insert, the tabs being configured to deflect radially inward when the insert is inserted into the container and resiliently pressed against the inner surface of the container. The insert includes two or more slits extending from the top end toward the bottom end in the wall of the body, wherein each of the slits separates two of the two or more resilient tabs.The body further includes one or more pawls at the tip of the insert, the one or more pawls being configured to engage with the inner surface of the container to secure the insert within the container. A first opening includes at least two first openings axially aligned in a first row on a first side of the body. A first opening includes at least two first openings axially aligned in a second row on a second side of the body, wherein the first row and the second row are opposite to each other on the body. A first opening consists only of the first openings in the first row and the second row. The insert includes two of one or more second openings, the first of which is located at the top of the first row, and the second of which is located at the top of the second row. A second opening consists of only two second openings. Only two second openings are spaced equidistant from the bottom end of the body. Only two second openings are spaced apart at different distances from the bottom end of the body. One or more second openings consist of only one second opening. Only one second opening is axially aligned with at least one of the plurality of first openings. The body includes one or more planar portions, and each of the first openings and the second openings is formed in one or more planar portions. The insert includes a first slit located entirely between the top and bottom ends of the body, wherein the first slit is longitudinally oriented and includes a length extending between the top and bottom ends of the body, the length being at least twice the length or diameter of each of the first openings, and the first slit is generally positioned closer to the top end than the one or more first openings. The length of the first slit is at least six times the length or diameter of each of the one or more first openings. 108. The length of the first slit is at least four times the length or diameter of each of the one or more first openings. The slit is disposed between and collinear with at least two of the first openings, and collinear with at least one of the first openings and one of the second openings and disposed between them. The length of the slit is approximately 6.0 times, approximately 5.0 to approximately 7.0 times, approximately 3.0 to approximately 10.0 times, or more than approximately 3.0 times the width of the slit. The length of the slit is approximately 12.0 mm, approximately 11.5 mm to approximately 12.5 mm, approximately 10.0 mm to approximately 15.0 mm, approximately 5.0 mm to approximately 20.0 mm, or more than approximately 5.0 mm. The width of the slit is substantially equal to the diameter or width of at least one of the first openings. The width of the slit is from about 1.0 mm to about 4.0 mm, from about 1.0 mm to about 3.0 mm, or about 2.0 mm. The insert includes a longitudinally oriented second slit, which is circumferentially and longitudinally offset from the first slit, wherein the length of the second slit is at least twice the length or diameter of each of the first openings. The first slit is positioned closer to the tip than the plurality of first openings.

[0009] On the other hand, this disclosure relates to a system for limiting liquid evaporation from a container, comprising a container defining a volume partially filled with liquid, the container defining an opening at a top of the container and having a top surface at a bottom of the container; and an insert extending within the container, wherein a first end of the insert is adjacent to the top of the container and a second end of the insert is adjacent to the top surface at the bottom of the container.

[0010] The liquid is disposed below at least one of the second openings and above most of the first opening. The liquid contains a solid support. The solid support is magnetically responsive particles or beads.

[0011] On the other hand, this disclosure relates to a method for dispersing components in a liquid, the method comprising agitating the container of the agitation system for a sufficient period of time to disperse the components in the liquid within the cavity and outside the insert.

[0012] The method of agitating the container includes moving the container around a circular path. The method includes removing a certain amount of liquid from the container after agitation. The method also includes agitating the container for a sufficient period of time after removing the liquid to disperse the components within the liquid. The method includes sensing the liquid level within the insert, comparing the sensed level to a threshold, and refilling the container with additional liquid or replacing the container if the sensed level is below the threshold. The method further includes using a pipette to perform the aspiration of a certain amount of liquid from the container, and before retrieval, the method includes capacitive or pressure-based liquid level detection with the pipette to confirm that the pipette or the pipette tip attached to the pipette has contacted the liquid and is at the position where the aspiration of a certain amount of liquid begins.

[0013] On the other hand, this disclosure relates to a mixing method comprising: continuously agitating a container of a stirring system for a sufficient period of time to mix a liquid within the cavity and outside an insert, wherein the liquid is a combination liquid comprising two or more liquids separately supplied to the container.

[0014] The method involves moving the container around a circular track. The method includes removing a quantity of the combined liquid from the container after agitation. The method further includes agitating the container to mix two or more liquids within the combined liquid after removing the quantity of the combined liquid. The method includes sensing the level of the combined liquid within the insert, comparing the sensed level to a threshold, and refilling or replacing the container with additional quantities of each of the two or more liquids if the sensed level is below the threshold. A quantity of the combined liquid is retrieved from the container using a pipette, and prior to retrieval, the method further includes capacitive or pressure-based level detection using the pipette to confirm that the pipette or the pipette tip attached to the pipette has contacted the combined liquid and is at the point where the quantity of the combined liquid is being drawn.

[0015] On the other hand, this disclosure relates to an insert for a liquid holding container, the insert comprising a body including a wall, an opening top end and a bottom end, a generally tubular inner cavity extending from the opening top end to the opening bottom end; one or more first openings formed in the wall, the first openings being located between the top end and the bottom end; and a longitudinally oriented first slit enclosed by the wall, the first slit having a length and a width, wherein the length of the first slit is at least twice the length or diameter of each of the first openings, and the entire first slit is disposed closer to the top end than at least one of the first openings.

[0016] The first slit is disposed between at least two of the first openings and is collinear with at least two of them. The length of the first slit is approximately 6.0 times, approximately 5.0 times to about 7.0 times, approximately 3.0 times to about 10.0 times, or more than approximately 3.0 times, the width of the first slit. The length of the first slit is approximately 12.0 mm, approximately 11.5 mm to about 12.5 mm, approximately 10.0 mm to about 15.0 mm, approximately 5.0 mm to about 20.0 mm, or more than approximately 5.0 mm. The width of the first slit is substantially equal to the width or diameter of at least one of the first openings. The width of the first slit is approximately 1.0 mm to about 4.0 mm, approximately 1.0 mm to about 3.0 mm, or about 2.0 mm. Each of the first openings is circular in shape. The diameter of each of the first openings is approximately 1.0 mm to about 4.0 mm, approximately 1.0 mm to about 3.0 mm, or about 2.0 mm. The diameter of each of the first openings is at least about 2.0 mm. The body tapers radially inward from the top to the bottom. The inner diameter of the body at the first end is larger than the inner diameter of the body at the bottom end. At least one first opening is located below the midpoint. The majority of the first opening is located between the midpoint and the bottom end. Two-thirds or more of the first opening is located between the midpoint and the bottom end. The insert includes at least one groove in a wall extending from the bottom end of the insert toward the top end. The at least one groove includes two opposing grooves, each extending from the bottom end toward the top end. The at least one groove is a recess in the bottom end of the insert. The body further includes two or more resilient tabs at the top end of the insert, the tabs being configured to deflect radially inward when the insert is inserted into the container and resiliently pressed against the inner surface of the container. The insert includes two or more additional slits extending from the top to the bottom end in the wall of the body, wherein each of the additional slits separates two of the two or more resilient tabs. The body further includes one or more pawls at the top end of the insert, the one or more pawls being configured to engage with the inner surface of the container to secure the insert within the container. The first opening includes at least two first openings axially aligned in a first row on a first side of the body. The first opening also includes at least two first openings axially aligned in a second row on a second side of the body, wherein the first and second rows are opposite to each other on the body. The first opening consists only of the first openings in the first and second rows. The first slit is collinear with either the first opening in the first row or the first opening in the second row. The body includes one or more planar portions, and each of the first openings and the first slit is formed in the planar portion. The insert includes a longitudinally oriented second slit that is circumferentially and longitudinally offset from the first slit. One or more first openings include a plurality of first openings. The first slit is positioned closer to the top than at least two of the plurality of first openings.

[0017] On the other hand, this disclosure relates to a system for limiting liquid evaporation from a container, comprising a container defining a volume partially filled with liquid, the container defining an opening at a top and having a top surface at a bottom; and an insert extending within the container, wherein the top of the insert is adjacent to the top of the container, and the bottom of the insert is adjacent to the top surface at the bottom of the container. The surface of the liquid is disposed between the top and bottom of the slit. The liquid contains a solid support. The solid support is a magnetically responsive particle or bead. The liquid is a combination liquid comprising a first liquid and a second liquid, the second liquid forming a gradient of the liquid surface adjacent to the insert within the first liquid.

[0018] On the other hand, this disclosure relates to a method of mixing contents within a container containing an insert, the container comprising a first liquid, the method comprising adding a second liquid to the container to form a combined liquid, the second liquid having a lower density than the first liquid, wherein after adding the second liquid to the first liquid, a surface of the combined liquid is disposed between the top and bottom ends of a first slit, and a gradient of the second liquid in the first liquid is disposed near the surface; agitating the combined liquid within the container to mix the first and second liquids within the cavity and outside the insert. Agitating the combined liquid includes moving the container about a track path. The track path is a circular track path. The method includes extracting a certain amount of the combined liquid from the container after agitating the combined liquid. The method includes agitating the container to promote mixing of the first and second liquids after extracting a certain amount of the combined liquid from the container. The method includes sensing the level of the combined liquid within the insert, comparing the sensed level to a threshold, and refilling the container with an additional amount of each of the first and second liquids and an additional amount of the second liquid, or replacing the container, when the sensed level of the combined liquid is below the threshold. A certain amount of the combined liquid is extracted from the container using an automated pipette, wherein the extraction includes aspirating a certain amount of the combined liquid. Prior to extraction, the method also includes capacitive or pressure-based level detection using a pipette to confirm that the pipette or the tip of the pipette fixed to the shaft of the pipette has contacted the combined liquid and is at the position where a certain amount of the combined liquid can be extracted.

[0019] This invention includes:

[0020] 1. An insert for a liquid holding container, the insert comprising:

[0021] The body includes a wall, an opening top end and an opening bottom end, and a generally tubular inner cavity extending from the opening top end to the opening bottom end;

[0022] A plurality of first openings are formed in the wall, the first openings being located between the top end and the bottom end, and each of the first openings defining an area; and

[0023] One or more second openings are formed in the wall, the one or more second openings being located between the top end and the bottom end, each of the one or more second openings defining an area larger than that defined by any one of the first openings, wherein at least one of the one or more second openings is located closer to the top end than any one of the first openings, and wherein each of the first openings and the second openings is sized to allow liquid to pass through.

[0024] 2. The insert according to claim 1, wherein the thickness of the wall immediately surrounding each of the first openings is greater than the thickness of the wall immediately surrounding each of the one or more second openings.

[0025] 3. The insert according to item 2, wherein the thickness of the wall immediately surrounding each of the first openings is from about 0.5 mm to about 1.5 mm.

[0026] 4. The insert according to item 2 or 3, wherein the thickness of the wall immediately surrounding each of the one or more second openings is from about 0.10 mm to about 0.40 mm.

[0027] 5. The insert according to item 2, wherein the thickness of the wall immediately surrounding each of the first openings is about 1.0 mm, and the thickness of the wall immediately surrounding each of the one or more second openings is about 0.25 mm.

[0028] 6. The insert according to any one of the preceding items, wherein the wall includes a chamfer around each of the one or more second openings.

[0029] 7. The insert according to item 6, wherein the chamfer is a four-sided chamfer.

[0030] 8. The insert according to any one of the preceding items, wherein each of the one or more second openings is collinear with at least two of the first openings.

[0031] 9. The insert according to any one of the preceding items, wherein each of the one or more second openings is rectangular or square in shape.

[0032] 10. The insert according to any one of the preceding items, wherein the width of each of the one or more second openings is about 2.0 mm to about 8.0 mm, about 2.0 mm to about 7.0 mm, about 2.0 mm to about 6.0 mm, about 3.0 mm to about 5.0 mm, about 4.0 mm or about 3.8 mm.

[0033] 11. The insert according to any one of the preceding items, wherein the width of each of the one or more second openings is at least about 2.0 mm.

[0034] 12. The insert according to any one of the preceding items, wherein each of the first openings is circular in shape.

[0035] 13. The insert according to any one of the preceding items, wherein the diameter of each of the one or more first openings is from about 1.0 mm to about 4.0 mm, from about 1.0 mm to about 3.0 mm, or about 2.0 mm.

[0036] 14. The insert according to any one of items 1 to 12, wherein the diameter of each of the one or more first openings is at least about 1.0 mm.

[0037] 15. The insert according to any one of the preceding items, wherein the ratio of the area of ​​any one of the one or more second openings to the area of ​​any one of the first openings is at least about 2.0.

[0038] 16. The insert according to any one of the preceding items, wherein the ratio of the area of ​​any one of the one or more second openings to the area of ​​any one of the first openings is about 2.0 to about 8.0, about 3.0 to about 6.0, about 3.5 to about 5.0, about 4.5 to about 4.6, or about 4.0.

[0039] 17. The insert according to any one of the preceding items, wherein the pressure required to remove a liquid film across any one of the one or more second openings is less than the pressure required to remove a liquid film across any one of the first openings.

[0040] 18. The insert according to any one of the preceding items, wherein the body tapers radially inward from the top end toward the bottom end.

[0041] 19. The insert according to any one of the preceding items, wherein the inner diameter of the body at the top end is greater than the inner diameter of the body at the bottom end.

[0042] 20. The insert according to any one of the preceding items, wherein at least one of the first openings is located below the midpoint of the body length.

[0043] 21. The insert according to any one of the preceding items, wherein a majority of the first opening is located below the midpoint of the body length.

[0044] 22. The insert according to any one of the preceding items, wherein two-thirds or more of the first opening is located below the midpoint of the body length.

[0045] 23. The insert according to any one of the preceding items, wherein each of the one or more second openings is located above the midpoint of the body length.

[0046] 24. The insert according to any one of the preceding items, further comprising at least one groove in the wall extending from the bottom end of the insert toward the top end.

[0047] 25. The insert according to item 24, wherein the at least one slot comprises two opposing slots, each extending from the bottom end toward the top end.

[0048] 26. The insert according to item 24, wherein the at least one groove is a recess in the bottom end of the insert.

[0049] 27. The insert according to any one of the preceding claims, wherein the body further includes two or more resilient tabs at the tip of the insert, the tabs being configured to deflect radially inward when the insert is inserted into the container and resiliently pressed against the inner surface of the container.

[0050] 28. The insert according to item 27 further includes two or more slits extending from the top end toward the bottom end in the wall of the body, wherein each of the slits separates two of the two or more resilient tabs.

[0051] 29. The insert according to claim 28, wherein the body further includes one or more pawls at the tip of the insert, the one or more pawls being configured to engage with the inner surface of the container to secure the insert within the container.

[0052] 30. The insert according to any one of the preceding items, wherein the first opening comprises at least two first openings aligned axially in a first row on a first side of the body.

[0053] 31. The insert according to item 30, wherein the first opening comprises at least two first openings axially aligned in a second row on a second side of the body, wherein the first row and the second row are opposite to each other on the body.

[0054] 32. The insert according to item 31, wherein the first opening consists only of the first openings of the first row and the second row.

[0055] 33. The insert according to item 31, wherein the insert comprises two of the one or more second openings, the first of the second openings being disposed at the top of the first row, and the second of the second openings being disposed at the top of the second row.

[0056] 34. The insert according to any one of the preceding items, wherein the second opening consists of only two second openings.

[0057] 35. The insert according to item 34, wherein only two second openings are spaced equidistant from the bottom end of the body.

[0058] 36. The insert according to item 34, wherein only the two second openings are spaced apart from the bottom end of the body by different distances.

[0059] 37. The insert according to any one of items 1 to 32, wherein the one or more second openings consist of only one second opening.

[0060] 38. The insert according to item 37, wherein the only second opening is axially aligned with at least one of the plurality of first openings.

[0061] 39. The insert according to any one of the preceding items, wherein the body includes one or more planar portions, and each of the first opening and the second opening is formed in the one or more planar portions.

[0062] 40. A system for limiting the evaporation of liquid from a container, comprising:

[0063] A container defining a volume partially filled with liquid, the container defining an opening at the top of the container and having a top surface at the bottom of the container; and

[0064] The insert according to any one of the preceding items extends within the container, wherein a first end of the body is adjacent to the top of the container, and a second end of the body is adjacent to the top surface at the bottom of the container.

[0065] 41. The system according to item 40, wherein the liquid is disposed below at least one of the second openings and above most of the first opening.

[0066] 42. The system according to claim 40 or 41, wherein the liquid contains a solid support.

[0067] 43. The system according to item 42, wherein the solid support is a magnetically responsive particle or bead.

[0068] 44. A method for dispersing a component in a liquid, the method comprising:

[0069] The container of the system according to item 40 is agitated for a sufficient period of time to disperse the components in the liquid within the inner cavity and outside the insert.

[0070] 45. The method of claim 44, wherein agitating the container comprises moving the container about an orbital path.

[0071] 46. ​​The method according to item 45, wherein the track path is a circular track path.

[0072] 47. The method according to any one of items 44 to 46, further comprising retrieving a certain amount of liquid from the container after agitating the container.

[0073] 48. The method according to item 47, further comprising, after retrieving the amount of liquid from the container, agitating the container for a sufficient period of time to disperse the components in the liquid.

[0074] 49. The method according to item 47 or 48, further comprising sensing the level of the liquid within the insert, comparing the sensed level with a threshold, and refilling the container with an additional amount of the liquid or replacing the container when the sensed level is below the threshold.

[0075] 50. The method according to any one of claims 47 to 49, wherein the retrieval of the volume of liquid from the container is performed using a pipette, and prior to retrieval, the method further includes capacitive or pressure-based level detection using the pipette to confirm that the pipette or the pipette tip attached to the pipette has contacted the liquid and at the position where the retrieval of the volume of liquid begins.

[0076] 51. A mixing method, the method comprising:

[0077] The container of the system according to any one of items 40 to 43 is agitated for a sufficient period of time to mix the liquid within the cavity and outside the insert, wherein the liquid is a combination liquid comprising two or more liquids separately supplied to the container.

[0078] 52. The method according to item 51, wherein agitating the container includes moving the container about an orbital path.

[0079] 53. The method according to item 52, wherein the track path is a circular track path.

[0080] 54. The method according to any one of items 51 to 53, further comprising retrieving a certain amount of the combined liquid from the container after agitating the container.

[0081] 55. The method according to item 54, further comprising, after retrieving the amount of combined liquid from the container, agitating the container to mix the two or more liquids in the combined liquid.

[0082] 56. The method according to item 54 or 55 further includes sensing the level of the combined liquid inside the insert, comparing the sensed level with a threshold, and refilling the container with an additional amount of each of the two or more liquids, or replacing the container, when the sensed level is below the threshold.

[0083] 57. The method according to any one of items 54 to 56, wherein the retrieval of the quantity of combined liquid from the container is performed using a pipette, and prior to retrieval, the method further includes capacitive level detection or pressure-based level detection using the pipette to confirm that the pipette or the pipette tip attached to the pipette has contacted the combined liquid and at the position where the retrieval of the quantity of combined liquid begins.

[0084] 58. The insert according to any one of items 1 to 39, further comprising a first slit located entirely between the top and bottom ends of the body, wherein the first slit is longitudinally oriented and includes a length extending between the top and bottom ends of the body, the length being at least twice the length or diameter of each of the first openings, and the first slit is configured to be closer to the top end than one or more of the first openings.

[0085] 59. The insert according to item 58, wherein the length of the first slit is at least four times the length or diameter of each of the first openings.

[0086] 60. The insert according to claim 58, wherein the length of the first slit is at least six times the length or diameter of each of the first openings.

[0087] 61. The insert according to any one of items 58 to 60, wherein the slit is disposed between at least two of the first openings and collinear with at least two of the first openings, or collinear with at least one of the first openings and one of the second openings and disposed between at least one of the first openings and one of the second openings.

[0088] 62. The insert according to any one of items 58 to 61, wherein the length of the slit is about 6.0 times, about 5.0 times to about 7.0 times, about 3.0 times to about 10.0 times, or more than about 3.0 times the width of the slit.

[0089] 63. The insert according to claim 62, wherein the length of the slit is about 12.0 mm, about 11.5 mm to about 12.5 mm, about 10.0 mm to about 15.0 mm, about 5.0 mm to about 20.0 mm, or more than about 5.0 mm.

[0090] 64. The insert according to any one of items 58 to 63, wherein the width of the slit is substantially equal to the diameter or width of at least one of the first openings.

[0091] 65. The insert according to claim 64, wherein the width of the slit is from about 1.0 mm to about 4.0 mm, from about 1.0 mm to about 3.0 mm, or about 2.0 mm.

[0092] 66. The insert according to any one of items 58 to 65, further comprising a longitudinally oriented second slit, the longitudinally oriented second slit being circumferentially and longitudinally offset from the first slit, wherein the length of the second slit is at least twice the length or diameter of each of the first openings.

[0093] 67. The insert according to any one of items 58 to 66, wherein the entire first slit is positioned closer to the top end than the plurality of first openings.

[0094] 68. An insert for a liquid holding container, the insert comprising:

[0095] The body includes a wall, an opening top end and an opening bottom end, and a generally tubular inner cavity extending from the opening top end to the opening bottom end;

[0096] One or more first openings are formed in the wall, the first openings being located between the top end and the bottom end; and

[0097] A longitudinally oriented first slit enclosed by the wall, the first slit having a length and a width, wherein the length of the first slit is at least twice the length or diameter of each of the first openings, and the entire first slit is positioned closer to the top than at least one of the first openings.

[0098] 69. The method according to item 68, wherein the first slit is at least four times larger in length or diameter than each of the first openings.

[0099] 70. The method according to item 68, wherein the first slit is at least six times larger in length or diameter than each of the first openings.

[0100] 71. The insert according to any one of items 68 to 70, wherein the first slit is disposed between at least two of the first openings and is collinear with at least two of the first openings.

[0101] 72. The insert according to any one of items 68 to 71, wherein the length of the first slit is about 6.0 times, about 5.0 to about 7.0 times, about 3.0 to about 10.0 times, or more than about 3.0 times the width of the first slit.

[0102] 73. The insert according to any one of items 68 to 72, wherein the length of the first slit is about 12.0 mm, about 11.5 mm to about 12.5 mm, about 10.0 mm to about 15.0 mm, about 5.0 mm to about 20.0 mm, or more than about 5.0 mm.

[0103] 74. The insert according to any one of items 68 to 73, wherein the width of the first slit is substantially equal to the width or diameter of at least one of the first openings.

[0104] 75. The insert according to claim 74, wherein the width of the first slit is about 1.0 mm to about 4.0 mm, about 1.0 mm to about 3.0 mm, or about 2.0 mm.

[0105] 76. The insert according to any one of items 68 to 75, wherein each of the first openings is circular in shape.

[0106] 77. The insert according to any one of items 68 to 76, wherein the diameter of each of the first openings is from about 1.0 mm to about 4.0 mm, from about 1.0 mm to about 3.0 mm, or about 2.0 mm.

[0107] 78. The insert according to any one of items 68 to 77, wherein the diameter of each of the first openings is at least about 2.0 mm.

[0108] 79. The insert according to any one of items 68 to 78, wherein the body tapers radially inward from the top end toward the bottom end.

[0109] 80. The insert according to any one of items 68 to 79, wherein the inner diameter of the body at the first end is greater than the inner diameter of the body at the bottom end.

[0110] 81. The insert according to any one of items 68 to 80, wherein at least one of the first openings is located below the midpoint.

[0111] 82. The insert according to any one of items 68 to 81, wherein a majority of the first opening is located between the midpoint and the bottom end.

[0112] 83. The insert according to item 82, wherein two-thirds or more of the first opening is located between the midpoint and the bottom end.

[0113] 84. The insert according to any one of items 68 to 83, further comprising at least one groove in the wall extending from the bottom end of the insert toward the top end.

[0114] 85. The insert according to item 84, wherein the at least one slot comprises two opposing slots, each extending from the bottom end toward the top end.

[0115] 86. The insert according to item 84 or 85, wherein the at least one groove is a recess in the bottom end of the insert.

[0116] 87. An insert according to any one of claims 68 to 86, wherein the body further includes two or more resilient tabs at the tip of the insert, the tabs being configured to deflect radially inward when the insert is inserted into the container and resiliently pressed against the inner surface of the container.

[0117] 88. The insert according to item 87, further comprising two or more additional slits extending from the top end toward the bottom end in the wall of the body, wherein each of the additional slits separates two of the two or more resilient tabs.

[0118] 89. The insert according to claim 88, wherein the body further includes one or more pawls at the tip of the insert, the one or more pawls being configured to engage with the inner surface of the container to secure the insert within the container.

[0119] 90. The insert according to any one of items 68 to 89, wherein the first opening comprises at least two first openings aligned axially in a first row on a first side of the body.

[0120] 91. The insert according to claim 90, wherein the first opening comprises at least two first openings axially aligned in a second row on a second side of the body, wherein the first row and the second row are opposite to each other on the body.

[0121] 92. The insert according to item 91, wherein the first opening consists only of the first openings of the first row and the second row.

[0122] 93. The insert according to item 92, wherein the first slit is collinear with the first opening of the first row or the first opening of the second row.

[0123] 94. The insert according to any one of items 68 to 93, wherein the body comprises one or more planar portions, and each of the first openings and the first slit is formed in the planar portion.

[0124] 95. The insert according to any one of items 68 to 94 further includes a second slit oriented longitudinally, said second slit being circumferentially and longitudinally offset from the first slit.

[0125] 96. The insert according to any one of items 68 to 95, wherein the one or more first openings comprise a plurality of first openings.

[0126] 97. The insert according to item 96, wherein the entire first slit is positioned closer to the top than at least two of the plurality of first openings.

[0127] 98. A system for limiting the evaporation of liquid from a container, comprising:

[0128] A container that defines a volume partially filled with liquid, the container defining an opening at the top and having a top surface at the bottom; and

[0129] An insert extending within the container according to any one of claims 69 to 94, wherein the top end of the body is adjacent to the top end of the container, and the bottom end of the body is adjacent to the top surface at the bottom end of the container.

[0130] 99. The system according to claim 98, wherein the surface of the liquid is disposed between the top and bottom ends of the slit.

[0131] 100. The system according to claim 99, wherein the liquid contains a solid support.

[0132] 101. The system according to claim 100, wherein the solid support is a magnetically responsive particle or bead.

[0133] 102. The system according to any one of claims 98 to 101, wherein the liquid is a combination liquid comprising a first liquid and a second liquid, the second liquid forming a gradient within the first liquid adjacent to the liquid surface within the insert.

[0134] 103. A method of mixing contents within a container comprising an insert according to any one of claims 68 to 97, the container containing a first liquid, the method comprising:

[0135] A second liquid is added to the container, thereby forming a combined liquid, the second liquid having a density lower than that of the first liquid, wherein after the second liquid is added to the first liquid, the surface of the combined liquid is disposed between the top and bottom ends of the first slit, and the gradient of the second liquid in the first liquid is disposed adjacent to the surface;

[0136] The combined liquids within the container are agitated, thereby mixing the first liquid and the second liquid within the inner cavity and outside the insert.

[0137] 104. The method according to claim 103, wherein agitating the combined liquid comprises moving the container about an orbital path.

[0138] 105. The method according to item 104, wherein the track path is a circular track path.

[0139] 106. The method according to any one of items 103 to 105, further comprising extracting a certain amount of the combined liquid from the container after agitating the combined liquid.

[0140] 107. The method according to claim 106 further includes, after extracting the amount of combined liquid from the container, agitating the container to promote mixing of the first liquid and the second liquid.

[0141] 108. The method according to item 106 or item 107, further comprising sensing the level of the combined liquid within the insert, comparing the sensed level with a threshold, and, when the sensed level of the combined liquid is below the threshold, refilling the container or replacing the container with additional amounts of each of the first liquid and the second liquid and additional amounts of the second liquid.

[0142] 109. The method according to any one of items 106 to 108, wherein the extraction of the amount of combined liquid from the container is performed using an automatic pipette, and wherein the extraction includes aspirating the amount of combined liquid.

[0143] 110. The method according to claim 109, wherein prior to extraction, the method further comprises capacitive or pressure-based level detection using the pipette to confirm that the pipette or the tip of the pipette fixed to the shaft of the pipette has contacted the combined liquid and at the position where extraction of the amount of the combined liquid begins. Attached Figure Description

[0144] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate various embodiments and, together with the description, serve to explain the principles of the disclosed embodiments.

[0145] Figure 1 This is a top perspective view of a liquid container mixing apparatus according to an embodiment of the present disclosure.

[0146] Figure 2 yes Figure 1 Bottom perspective view of the device.

[0147] Figure 3 yes Figure 1 A schematic diagram of the power and control system of the equipment.

[0148] Figure 4 yes Figure 1 A schematic diagram of the orbital movement of a part of the device.

[0149] Figure 5 This is a perspective view of an insert according to an embodiment of the present disclosure.

[0150] Figure 6-8 yes Figure 5 Side view of the insert.

[0151] Figure 9 It is along Figure 8 The cross-sectional view of the insert is taken from line 9-9.

[0152] Figure 10 yes Figure 9 An enlarged view of a portion of the cross-sectional view.

[0153] Figure 11 This is a cross-sectional view of the insert and container according to an embodiment of the present disclosure.

[0154] Figure 12 This is a cross-sectional view of the insert, container, and pipette tip according to embodiments of the present disclosure.

[0155] Figure 13 This is a flowchart of a method according to an embodiment of the present disclosure.

[0156] Figure 14 yes Figure 11 The cross-sectional view of the insert and container shows the gradient in the liquid solution or suspension within the insert.

[0157] Figure 15 This is a side view of the insert according to another embodiment of the present disclosure.

[0158] Figure 15A yes Figure 15 Cross-sectional view of the insert and container.

[0159] Figure 16 This is a side view of the insert according to yet another embodiment of the present disclosure.

[0160] Figure 16A yes Figure 16 Cross-sectional view of the insert and container.

[0161] Figure 17-19 This is a dot plot of fluorescence measurements performed under various conditions, showing the effect of concentration gradients in liquid solutions or suspensions on measurements dependent on the liquid solution or suspension, such as... Figure 14 The gradient shown.

[0162] Figure 20 This is a bar graph comparing the evaporation rates of various inserts from this disclosure. Detailed Implementation

[0163] Reference will now be made in detail to embodiments of the present disclosure illustrated in the accompanying drawings. Where possible, the same reference numerals will be used throughout the drawings to refer to the same or similar parts. In the following discussion, relative terms such as “about,” “substantially,” “approximately,” etc., are used to indicate possible variations of ±10% in the stated numerical values.

[0164] mixing equipment

[0165] Figure 1-3 A liquid container mixing apparatus 100 is shown. The apparatus 100 may include a container support platform 101 configured to hold one or more liquid containers. In the illustrated embodiment, the container support platform is rotatable about an axis of rotation (e.g., at the center of the platform). The container support platform 101 may include a container tray 110 configured to hold a plurality of liquid containers 126, 128, and 130, and a turntable 150 mounted, otherwise attached, or integrated with the container tray 110. Figure 2 (as shown in the image).

[0166] Platform 101 is also configured to move in a track path about a track center, which, for example, is offset from the center of platform 101. In the context of this specification, when used to describe the movement of platform 101 (liquid container tray 110 and turntable 150), the terms track, orbit, or similar terms may refer to the path of movement, whereby the entire platform 101 moves about the track center independently of the rotation or spin of the liquid container support platform 101 about the axis of rotation of platform 101. Figure 4 The orbital motion of turntable 150 is illustrated. During this orbital motion, turntable 150 is movable such that the center of turntable 150 revolves around the center of the orbit C. OThe circle centered on C V It moves along a track. When turntable 150 moves through positions 1501, 1502, 1503, and 1504, the center of turntable 150 moves through positions C1, C2, C3, and C4.

[0167] The device 100 may also include a turntable drive system 200 connected to the platform 101. Figure 2 (As shown in the diagram). The turntable drive system 200 is configured and arranged to cause rotation or indexing of the liquid container support platform. In the illustrated embodiment, the turntable drive system 200 allows the platform 101 to rotate about a rotation axis at the center of the platform 101. The device 100 may also include a drive system 300 coupled to the liquid container support platform. (As shown in the diagram). Figure 4 As described, the drive system 300 is configured to cause the platform 101 to move along its track.

[0168] The turntable drive system 200 and drive system 300 can operate independently of each other, allowing the platform 101 (container tray 110 and turntable 150) to rotate independently about a central axis of rotation, or to move about one or more track axes. The turntable drive system 200 and drive system 300 can also operate simultaneously to allow the platform 101 to rotate and move simultaneously about track paths, which can improve the mixing of the contents of the containers 126, 128, and / or 130 contained within the container tray 110.

[0169] like Figure 1 and Figure 2 As shown, container tray 110 may include a plurality of cup-shaped, generally cylindrical container receiving portions having varying dimensions, such as a larger container receiving portion 112 and a smaller container receiving portion 116, configured to receive and hold liquid containers (e.g., bottles) 126, 128, and 130 of different sizes. Additionally, to accommodate different container sizes, separate insert adapters may be provided for receiving portions 112, 116. The adapters allow liquid containers to be introduced and secured in receiving portions 112, 116, having a diameter smaller than the diameter of receiving portions 112, 116. Container tray 110 may be circular in shape, and container receiving portions 112, 116 may be symmetrically arranged about a central axis of container tray 110. Container tray 110 may be formed of any suitable material, and in one embodiment, it is formed of molded plastic.

[0170] like Figure 2As shown, turntable 150 may include a disk configured to rotate about a central axis. In other embodiments, turntable 150 may have another shape configured to rotate about an axis substantially perpendicular to a plane of turntable 150. Turntable 150 may be formed of any suitable material having sufficient strength, rigidity, and machinability and being lightweight. Suitable exemplary materials include aluminum, stainless steel, or suitable plastics, including, for example, polystyrene, polyvinyl chloride (PVC), polypropylene, and polyethylene.

[0171] The turntable drive system 200 may include a turntable drive motor 202 coupled to the platform 101. Additionally, the turntable drive system 200 may be substantially similar to the turntable drive system described in U.S. Patent Application Publication No. 2014 / 0263163.

[0172] Figure 3 This is a schematic diagram of a control system for controlling the operation of device 100. As described above, device 100 can be configured to provide independent or simultaneous rotation and / or orbital movement of the container around a central axis to agitate the contents of the container. The rotation of turntable 150 in... Figure 3 The rotation of turntable 150 around center C is indicated by arrow R. The rotation of turntable 150 can be powered by drive system 200, particularly by drive motor 202. Track movement is powered by drive system 300, which includes motor 302. Drive motors 202 and 302 can be coupled to and controlled by controller 802, which is also connected to a controllable power supply 814. Controller 802 can provide power and operational control signals to drive motors 202 and 302. Controller 802 can also receive data from drive motors 202 and 302 in the form of rotary encoder counts and other feedback sensor signals. Feedback sensor 808 can be coupled to device 100 and may include, for example, rotation initial flags, position initial flags, etc. Sensor 808 can be connected to controller 802 to provide position or other status feedback, which is used to generate control signals for operating drive motors 202 and 302.

[0173] Evaporation limiting insert

[0174] The liquid contents of containers 126, 128, and 130, supported on container tray 110 of mixing device 100, may include liquid solutions or suspensions. Representative liquid contents may contain reagents with solid supports, such as silica or magnetically responsive particles or beads. See, for example, U.S. Patent Nos. 5,234,809 and 6,534,273. Solid supports may have a diameter of about 0.68 to about 1.00 μm. Such solid supports can be used to immobilize nucleic acids in sample processing procedures to remove inhibitors for amplification and / or detection. Other suitable reagents include, for example, target-enhancing reagents for alkaline shock treatments, as described in U.S. Patent No. 8,420,317. Reagents may be substances or mixtures for chemical analysis or other reactions. As discussed elsewhere in this disclosure, mixing of liquid contents (e.g., by agitation of containers containing liquid contents) can help maintain a suspension of suspended material within the liquid and / or resuspend material that has precipitated or otherwise detached from the solution / suspension. Other suitable reagents may include those from Thermo Fisher Scientific. Provided Nucleic acid purification kits and those described in U.S. Patent Application Publication No. 2006 / 0084089.

[0175] Even in the absence of suspended particles or solid supports, one or more components of a liquid solution may precipitate out of the solution, potentially affecting the concentration of the solution in the extraction container. Specifically, evaporation can occur within the insert 400, thereby increasing the concentration of the solution within the insert 400. Even small changes in concentration can adversely affect tests or determinations performed using such solutions.

[0176] The container can be carried in an open state to allow rapid access to the liquid contents of each container by a pipetting device (such as a robotic pipette). In other embodiments, the container may be sealed and / or include a filter or septum to limit aerosol dispersion of the reagent and further control reagent evaporation. The pipetting device can access the liquid contents of the container to remove liquid from the container and / or dispense additional liquid into the container. The pipetting device may include a pipette configured to detect the liquid surface within the container, for example, to determine or verify the liquid level within the container, which can be used to calculate the volume of liquid remaining in the container. A suitable pipette for this purpose is disclosed in U.S. Patent No. 6,914,555. Horizontal sensing, including, for example, capacitive horizontal sensing, may also be used to signal the initiation of an aspiration step, or to signal the start of an aspiration step to retrieve at least a portion of the liquid contents of the container. For example, once a liquid surface is detected, the pipette may continue along a downward path when aspirating liquid from the container. Alternatively, after detecting a liquid surface, the pipette may descend a predetermined distance before initiating aspiration. In the latter method, the pipette can be held stationary during aspiration. The pipette can employ at least one or more of capacitive level detection (cLLD) and pressure-based level detection (pLLD). Capacitive level detection can be performed using a conductive disposable pipette tip mounted on a tip holder of the pipette.

[0177] When a container is open, its liquid contents are exposed to the atmosphere and are therefore prone to evaporation. Mixing can exacerbate this problem because it increases the surface area of ​​the liquid exposed to the atmosphere, potentially accelerating the evaporation rate.

[0178] Figure 5-12 Showing methods for reducing the amount of gas from containers (e.g., Figure 11 and 12 The container 600 shown has an evaporation limiting insert 400 for limiting evaporation. The insert 400 may include a body 402 having a wall 403 extending from a first (top) end 404 toward a second (bottom) end 406. The inner cavity 408 ( Figure 11 and 12 (As shown) It can extend from the first end 404 through the body 402 to the second end 406. The first end 404 and the second end 406 can each be open and communicate with the cavity 408. The first end 404 and the second end 406 can be spaced apart from each other by about 95.0 mm to about 105.0 mm, or spaced apart by about 103.0 mm, but other suitable dimensions are also contemplated. In some embodiments, the insert 400 can encompass a volume of 280 mL, but other suitable volumes are also contemplated. Figure 5-12In the illustrated embodiment, the body 402 is tapered, having a dimension, such as diameter, that decreases from the first end 404 toward the second end 406, such that the diameter of the body 402 is larger at the first end 404 than at the second end 406. In one embodiment, the body 402 may have a diameter or width from about 17.6 mm to about 19.2 mm at the first end 404, but other suitable dimensions, both larger and smaller, are also contemplated. At the second end 406, the body 402 may have a diameter or width from about 13.4 mm to about 15.4 mm or about 14.4 mm, but other suitable dimensions, both larger and smaller, are also conceivable. In some embodiments, the body 402 may be substantially tubular or cylindrical.

[0179] Insert 400 is injection moldable. The mold may contain two halves and a core pin forming the center. Side holes may be formed by the two halves of the mold. To release insert 400, the core pin can be removed, and the two halves can be opened. Insert 400 may be adhered to one side of the mold, and an ejector pin may be used to push insert 400 out of the mold.

[0180] Body 402 may include one or more inert materials, including, for example, inert plastics that do not immerse themselves in the liquid contained within container 600. Additionally, it is preferred that the liquid does not degrade the materials used to form insert 400 or container 600 (i.e., the selected plastic or other material has chemical compatibility with the liquid it is intended to be used with). In one embodiment, the caps of insert 400 and container 600 comprise polypropylene (PP), and container 600 comprises high-density polyethylene (HDPE), but other suitable polymers and / or plastics are also contemplated.

[0181] The tapered shape of the body 402 can be roughly adapted to the shape of the pipette tip, for example, Figure 12 The pipette tip 700 is shown. This arrangement further limits evaporation from the container 600, as the liquid level may drop as it is retrieved from the container 600 via the insert 400, and the liquid surface area within the insert 400 and exposed to the atmosphere may become increasingly smaller. However, in some applications, the potential benefits of tapering to reduce evaporation may need to be balanced with the need to prevent contact between the insert 400 and the pipette tip 700. If a pipette-based level sensing is employed, contact between the pipette tip and the container insert could signal an incorrect position of the liquid surface, and the correlation analyzer might prematurely initiate the aspiration step before the pipette tip actually contacts the liquid surface.

[0182] The body 400 may include a plurality of openings extending through the wall 403. Each of the plurality of openings may extend into the cavity 408. The body 400 may include openings in a first row 410. Figure 6 and 9 ) and the second row 412 opening ( Figure 5 , Figure 8 and Figure 9 (As shown in the diagram). The first row 410 and the second row 412 may each include one or more first openings 414 and / or one or more second openings 416. The openings may be through holes. At least one of the first openings 414 may be below the midpoint of the height (or length measured along the axis) of the body 402. In other embodiments, at least half of the first openings is below the midpoint. In other embodiments, at least two-thirds of the first openings is below the midpoint. In other embodiments, all of the first openings 414 are below the midpoint. Each second opening 416 may be located above the midpoint 460, which is located at an intermediate position between the first end 404 and the second end 406. In some embodiments, each of the first openings 414 and / or second openings 416 of a given row (e.g., the first row 410 and the second row 412) may be collinear and / or longitudinally aligned. In other embodiments, one or more of the first openings 414 and / or second openings 416 of a given row may be offset from other openings of the given row. The first row 410 may be disposed within a flat surface 418 recessed from the outer surface of the wall 403, and the first row 412 may be disposed within a flat surface 420 recessed from the outer surface of the wall 403. The flat surfaces 418 and 420 facilitate the formation of openings 414 and 416 during the molding of the insert 400. Although in Figure 5-12 Two rows are shown in the embodiments, but in some embodiments, only one of the first row 410 and the second row 412 may be present, or an additional row of openings may be used. Any suitable number of first openings 414 and / or second openings 416 may be included on the insert 400. However, while a larger number of openings may improve mixing within the insert 400 and container 600, a larger number of openings may also increase evaporation relative to a design with fewer openings. It is also conceivable that at least one opening may be positioned below the liquid line of the reagent within the container 600 to facilitate reagent mixing.

[0183] The first opening 414 of the first row 410 and the second row 412 closest to the second end 406 is approximately 16.0 mm away from the second end 406, as measured from the center of the respective opening to the terminal portion of the first end 404 or the second end 406. Additionally, adjacent first openings 414 are approximately 16.0 mm away from each other, as measured between the centers of adjacent first openings 414. The second opening 416 of row 412 is approximately 16.0 mm away from the adjacent first opening 414, approximately 64.0 mm from the second end 406, and approximately 39.0 mm from the top first end 404. The second opening 416 of row 410 is approximately 13.0 mm away from the adjacent first opening 414, approximately 77.0 mm from the second end 406, and approximately 26.0 mm from the first end 404. Other values ​​of the dimensions described in this paragraph may also be used.

[0184] The first row 410 and the second row 412 can be located on opposite sides of the body 402, for example, they can be arranged 180 degrees apart from each other around the circumference of the body 402, but other spacing arrangements are also conceivable. A given opening of the first row 410 can be circumferentially aligned (at the same height) and / or aligned with the diameter of the opening of the second row 412 (separated by 180 degrees), or vice versa. Reference Figure 6 and 8 The three first openings 414 of the first row 410 closest to the second end 406 can be aligned circumferentially and diametrically with the three first openings 414 of the second row 412 closest to the second end 406. Furthermore, the second opening 416 of the second row 412 can be aligned circumferentially and diametrically with the first openings 414 of the first row 410. Figure 8 The first opening 414 and / or the second opening 416 can be seen through the second opening 416 of the second row 412. It is also conceivable that some first openings 414 and / or second openings 416 may not be aligned circumferentially or diametrically with another first opening 414 or second opening 416. For example, the second opening 416 of the first row 410 is not aligned circumferentially or diametrically with any other first opening 414 or second opening 416.

[0185] The first opening 414 may be circular, but any other suitable shape may be used, such as rectangular, square, rhomboid, oval, irregular, etc. The first opening 414 may have any suitable diameter or width. In one embodiment, the diameter or width of the first opening 414 may be from about 1.0 mm to about 4.0 mm, from about 1.0 mm to about 3.0 mm, or about 2.0 mm. In one embodiment, the diameter or width of the first opening 414 may be at least about 1.0 mm. Each first opening 414 of the insert 400 may have substantially the same dimensions as the other first openings 414 (considering manufacturing variability), or the various first openings 414 may have different dimensions. For example, some first openings 414 may have a diameter of about 2.0 mm, while other first openings 414 may have a diameter of about 3.0 mm. In another embodiment, the diameter of the first opening 414 may be increased or decreased as it moves from a first end 404 to a second end 406 of the insert 400.

[0186] The second opening 416 can be as follows: Figure 5 , 6The second opening 416 may be square as shown in Figure 8, but any other suitable shape may be used, such as rectangle, circle, rhombus, oval, irregular, etc. The second opening 416 may have any suitable diameter or width. The diameter or width of the second opening 416 may be greater than the diameter or width of at least one first opening 414, or may be greater than the diameter or width of all first openings 414. In one embodiment, the diameter or width of the second opening 416 may be from about 2.0 mm to about 8.0 mm, from about 2.0 mm to about 7.0 mm, from about 2.0 mm to about 6.0 mm, from about 3.0 mm to about 5.0 mm, about 4.0 mm, or about 3.8 mm. In one embodiment, the diameter or width of the second opening 416 may be at least about 2.0 mm. Each second opening 416 of the insert 400 may have substantially the same dimensions as the other second openings 416 (considering manufacturing variability), or the various second openings 416 may have different dimensions. Within a given row (e.g., first row 410 and second row 412), the second opening 416 may be positioned closer to the first end 404 than any of the first openings 414. However, it is also conceivable that one or more rows of openings may not include any of the second openings 416.

[0187] The area of ​​the second opening 416 may be approximately 2.0 to approximately 8.0 times, approximately 3.0 to approximately 6.0 times, approximately 3.5 to 5.0 times, or approximately 4.0 times the area of ​​the first opening 414. In another embodiment, the area of ​​the second opening 416 may be approximately 4.5 to approximately 4.6 times the area of ​​the first opening 414. In yet another embodiment, the area of ​​the second opening 416 may be at least approximately 2.0 times, at least approximately 2.5 times, at least approximately 3.0 times, at least approximately 3.5 times, at least approximately 4.0 times, or at least approximately 4.5 times larger than the area of ​​the first opening 414.

[0188] The thickness of wall 403 can be reduced in the region defining the second opening 416. For example, as Figure 10 As most clearly seen, the thin boundary 422 of wall 403 may surround the periphery of the second opening 416. The thin boundary may be about 0.10 mm to 0.40 mm thick, about 0.20 mm to about 0.30 mm thick, or about 0.25 mm thick. Wall 403 may move away from boundary 422 and increase in thickness. Flat surfaces 418 and 420 may each have a thickness of about 0.5 mm to about 1.5 mm or about 1.0 mm, but other suitable values ​​are contemplated. Apart from the thin boundary 422, the remainder of wall 403 may have the same thickness as flat surfaces 418 and 420. In some embodiments, the four sides of the square opening 416 may be defined by four chamfers 424. Boundary 422 may be in a plane, and chamfer 424 may include an angled portion extending radially outward relative to the plane at an angle α. Angle α may be from about 12 to about 18 degrees, from about 14 to about 16 degrees, or about 15 degrees, or may be another suitable angle.

[0189] It is also conceivable that the thin boundary could be formed by other suitable methods that do not include the gradual slope of the remaining thickness from wall 403. For example, boundary 422 could be formed by stamping wall 403 in the region surrounding the second opening 416 to form a thinned and stepped boundary region.

[0190] The larger width and area of ​​the second opening 416, the thinner boundary surrounding the second opening 416, and the square shape of the second opening 416 help prevent the formation of a liquid film on the second opening 416, require less force to overcome a formed film, and / or prevent clogging of the second opening 416, which in turn prevents the formation of a vacuum within the container 600 and the insert 400. The square shape and / or larger diameter / size of the second opening 416 increase the distance a film must traverse, reducing the likelihood of any film forming on the second opening 416 and decreasing the force required to overcome any film forming in the square second opening 416. Furthermore, the thin boundary surrounding the second opening 416 reduces the area where liquid can collect and form a film or otherwise block the second opening 416. The likelihood of a film forming on the second opening 416 is further reduced when the top level of the liquid within the container is below the second opening 416. In some embodiments, the second opening 416 may be located at different distances relative to the first end 402. In such embodiments, the top level of the liquid may be above one of the second openings 416 and below the other of the second openings 416.

[0191] The insert 400 may include one or more axial grooves 430 extending from the second end 406 toward the first end 404. The grooves 430 may have any suitable dimensions. For example, the grooves 430 may have a length of, for example, about 7.0 to about 9.0 mm, about 8.0 mm, or another suitable length. In one embodiment, the insert 400 may include two diameter-opposing grooves 430 spaced 180 degrees apart from each other. In another embodiment, the insert 400 may include only one groove 430 or two or more grooves 430. When multiple grooves 430 are used, they may be spaced apart from each other evenly or unevenly. The grooves 430 may be as follows: Figure 5 , 6 As shown in Figure 8, the tank 430 is wider at one end (e.g., the bottom end at the second end 406) than at the opposite end (e.g., the top end closer to the first end 404). In some embodiments, the tank 430 may be maintained below the dead volume of the liquid within the container, which may be the volume of the container that is no longer used by the automated analyzer. That is, when the volume within the container is at or below the dead volume (or minimum volume threshold), the container can be refilled with more reagent or completely replaced.

[0192] In various embodiments, the insert 400 may include one or more resilient tabs 436 defined by one or more slits 438 extending from the first end 404 toward the second end 406. The tabs 436 may be configured to respond to radially inwardly pointing forces (e.g., when the insert 400 is inserted into...). Figure 11 and 12 When the insert 400 is in the opening of the container 600 shown, it flexes radially inward. When flexed radially inward, the tabs may apply a radially outward force that helps secure the insert 400 within the container 600. In addition to or alternatively to the tab and slit arrangements described above, the insert 400 may include one or more pawls (not shown) that engage an inner surface of the container 600, including the pawls described in U.S. Patent Application Publication No. 2014 / 0263163. For example, one or more pawls may engage a corresponding recess on the inner surface of the container 600. Other suitable retention features are also contemplated, including, for example, snap-fit ​​arrangements, friction-fit arrangements, latches, etc. In some embodiments, one or more of the tabs 436 may include a chamfered top surface 439. The chamfered top surface 439 may facilitate the insertion of a pipette tip or other material device into the container 600. Without a bevel, when the pipette tip 700 is guided into the insert 400, the pipette tip 700 may come into contact with the top shoulder of the insert 400.

[0193] Containers and inserts

[0194] exist Figure 11 and 12 In the diagram, insert 400 is shown located within container 600. Insert 400 is inserted into container 600 through opening 602 at the top of neck 604. Figure 11 and 12 As shown, the first end 404 of the insert 400 may be disposed adjacent to the neck 604 of the container, and the second end 406 of the insert 400 may contact the bottom surface 606 of the container 600. The groove 430 of the container insert 400 prevents the bottom second end 406 of the insert 400 from forming a sealing contact with the bottom surface 606 of the container 600.

[0195] In various embodiments, when the insert 400 is fully inserted into the container 600, the lower ends of each slit 438 of the separating pair of tabs 436 may extend below the neck 604 of the container 600, thereby forming a small vent below the neck 604 of the container 600. The small vent helps prevent the formation of a vacuum in the container 600 and allows air to escape from the container 600 when it is filled with liquid. The elasticity of the tabs 436 or the biasing of the tabs in the radially outward direction can push the tabs 436 against the inner surface 605 of the neck 604 of the container 600 to secure the insert 400 within the container 600.

[0196] The openings 414 and 416 and the groove 430 of the insert 400 allow liquid (including particles or beads in a suspension) within the container 600 to flow between the space within the insert 400 (e.g., the cavity 408) and the space outside the insert 400 within the container 600. The second opening 416 resists membrane formation and helps prevent a vacuum from forming inside the container 600. This helps ensure that the liquid level 610 within the insert 400 is substantially at the same height as the liquid level 612 outside the insert 400 and within the container 600.

[0197] refer to Figure 14 A gradient 1402 may be formed within the insert 400 disposed within the container 600. Gradient 1402 may be formed when a substance is added to a liquid already disposed within the container 600 and the insert 400. The added substance may be any material added to the liquid, except for the liquid itself. Gradient 1402 may remain within the insert 400 even after a mixing process has been performed, for example, by the liquid container mixing apparatus 100 described above. Gradient 1402 may be generated by the density difference between the added substance and the liquid and / or by limited liquid exchange between the added substance and the liquid contained within the insert 400 and the container 600. In addition to the gradient, this disclosure also contemplates that a bilayer may be formed within the insert 400 when, for example, the added substance is a liquid having a lower density than the liquid already present in the insert 400 and the container 600, or when the added substance has low miscibility with the liquid already present in the insert 400 and the container 600. In one embodiment, the liquid may be a reagent used to perform a process or reaction in an analytical test. In some embodiments, the added substance may be an internal control reagent used to minimize the risk of false negative results in analytical tests due to inhibition. The internal control reagent may have a lower density than the liquid in insert 400. The internal control may also be used for calibration in analytical tests, starting from a known concentration. In one embodiment, the liquid may contain a solid support material, such as magnetically responsive particles that can be used to isolate and purify sample handling procedures for the analyte of interest. Examples of such procedures are disclosed in U.S. Patent Nos. 5,234,864, 6,110,678, and 9,051,601.

[0198] Gradient 1402 may exhibit a higher concentration of added substance immediately below liquid level 610 within insert 400. In some embodiments, gradient 1402 may not extend the entire length of the liquid-containing portion of insert 400. In these embodiments, the added substance in the liquid may be displaced substantially uniformly away from liquid level 610 within insert 400.

[0199] A higher concentration of the additive immediately below the liquid surface 610 may affect subsequent processes or reactions that depend on the uniform distribution of the additive in the liquid. For example, a high concentration of the additive in gradient 1402 may have the greatest impact on the process or reaction using the liquid when aspirating aliquots close to the initial liquid level 610, where this impact may decrease with subsequent aliquots of the liquid aspirated from container 600. It is also conceivable that later processes or reactions may be affected. For example, due to the high initial concentration of the additive at the top of gradient 1402, the concentration of the additive in the remaining portion of the liquid may be lower than expected. Therefore, later processes or reactions using these remaining portions of the liquid may have too little (or no) additive. Furthermore, it is conceivable that the initial aspiration of the liquid may originate from a location significantly below the liquid level 610 within insert 400 (e.g., at or near the bottom surface 606), meaning that the first aliquot of the liquid may have an insufficient concentration of additive.

[0200] Figure 15 and Figure 15A Insert 1500 is shown. Insert 1500 may be substantially similar to insert 400, except that a first opening 414 of the first row 410 may be replaced by a longitudinally oriented slit 1514. The longitudinally oriented slit may have a width greater than the width (along the longitudinal axis of insert 1500) than the width (along the axis perpendicular to the longitudinal axis of insert 1500). Unlike the slit 438 described above, slit 1514 may be enclosed at a top end 1514a located closer to the first end 404 of insert 1500, and at a bottom end 1514b located closer to the second end 406 of insert 1500. In the container into which insert 1500 will be inserted, slit 1514 may be positioned relative to a desired initial liquid level (e.g., ...). Figure 15A The liquid level 610 in the container 600 shown is positioned on the insert 1500. The slit 1514 can also be positioned and sized to provide increased exposure of the added material to the liquid inside the container 600 while minimizing evaporation. The slit 1514 is positioned such that a portion of the slit 1514 is below the liquid level 610, and another portion of the slit 1514 is above the liquid level 610 (see reference). Figure 15A This helps ensure adequate mixing of liquids (e.g., liquid solutions or suspensions) contained inside and outside the insert 1500. Figure 15In the illustrated embodiment, slit 1514 may be positioned entirely below midpoint 460, closer to the second end 406 than the first end 404, wherein midpoint 460 is equidistant between the uppermost edge of the insert 400 at the first end 404 and the lowermost edge of the insert 400 at the second end 406. It is also contemplated that midpoint 460 may be positioned closer to the second end 406 than at least a portion of slit 1514 (e.g., midpoint 460 may be closer to the second end 406 than a small portion of the length of slit 1514, a large portion of the length of slit 1514, or the entire length of slit 1514). In other words, all or at least a portion of slit 1514 may be located above midpoint 460. These described positions are merely exemplary. In practice, the positioning of slit 1514 on insert 1500 may be adjusted based on the expected initial liquid level in the container where insert 1500 is ultimately deployed. For example, the midpoint of slit 1514 may correspond to the expected initial liquid level in the container where insert 1500 is used. However, because the slit has a longer length than, for example, the first opening 414, the slit 1514 allows for some variability in the initial liquid level (e.g., the liquid level may be higher or lower than expected). This can be important because if there is no opening or slit adjacent to the liquid level 610, then insufficient mixing of the initial liquid and the added substance may occur.

[0201] Slit 1514 may be collinear with the remaining first openings 414 of the first row 410. In other embodiments, one or more slits 1514 may not be collinear with any of the first openings 414. For example, a plurality of circumferentially spaced slits 1514 may be provided on the insert 1500. The circumferentially spaced slits may be positioned at staggered heights to accommodate different initial liquid surface heights within the insert 1500, and / or to accommodate a decrease in the height of the liquid surface 610 as the liquid is retrieved / absorbed. In one embodiment, the length of the slit 1514 may be twice the length or diameter of a given first opening 414, but other ratios are also contemplated, including, for example, 3, 4, 5, 6, or greater. Additionally, as Figure 15 As shown, the midpoint of slit 1514 may be closer to the adjacent first opening 414 below slit 1514 (towards the first end 404) than the adjacent first opening 414 above slit 1514. In other embodiments, the midpoint of slit 1514 may be closer to the adjacent opening above slit 1514 than the adjacent opening below slit 1514, or the adjacent first openings 414 above and below slit 1514 may be equidistant. Again, these embodiments are merely exemplary. In yet another embodiment, there may be no first opening 414 or second opening 416 positioned above slit 1514, or only a second opening 416 positioned above slit 1514 may exist (and no first opening 414).

[0202] The dimensions shown below are for illustrative purposes only. Furthermore, the dimensions of the slit 1514 may be configured to accommodate a solid support in the liquid suspension. Additionally, the length of the insert 400 and the number and positioning of the first openings 414 may depend on the height of the container 600, the diameter of the neck of the container 600, and the initial intended height of the liquid in the container 600. To limit evaporation, one objective may be to limit the size and number of openings (e.g., the first opening 414, the second opening 416, and the slit 1514). The bottom end 1514b may be positioned at approximately 38.0 mm from the bottom edge of the second end 406, approximately 37.5 mm to approximately 38.5 mm from the bottom edge of the second end 406, or another suitable distance. The top end 1514a may be positioned at approximately 50.0 mm from the bottom edge of the second end 406, approximately 49.5 mm to approximately 50.5 mm from the bottom edge of the second end 406, or another suitable distance. Therefore, the slit 1514 may have a length of about 12.0 mm, from about 11.5 mm to about 12.5 mm, from about 10.0 mm to about 15.0 mm, from about 5.0 mm to about 20.0 mm, from about 5.0 mm or more, or another suitable length. The slit 1514 may also have a width of about 2.0 mm, from about 1.5 mm to about 2.5 mm, from about 1.0 mm to about 4.0 mm, from about 1.0 mm to about 3.0 mm, or another suitable width. For example... Figure 15 As shown, the slit 1514 is flexible at its top end 1514a and bottom end 1514b, such that the slit 1514 is generally elliptical in shape, or rectangular with rounded corners, but other suitable shapes, such as strictly rectangular, are also conceivable. The length of the slit 1514 can be about 6.0 times, about 5.0 times to about 7.0 times, about 3.0 times to about 10.0 times, or more than about 3.0 times, longer than the width of the slit 1514.

[0203] Figure 15 The illustrated embodiment includes a second opening 416 and a chamfer 424. The second opening 416 may be square, and the four sides of the second opening 416 may be defined by the four-sided chamfer 424. (The above is in contrast to...) Figure 6 Further details regarding the second opening 416 and the chamfer 424 are described. In some embodiments, except that there is no second opening 416, Figure 16 and 16A The insert 1600 shown may be substantially similar to the insert 1500 described above.

[0204] Inserts 1500, 1600 may include one or more first openings 414 located below slit 1514. The first openings 414 facilitate mixing within the container 600 and inserts 1500, 1600. The first openings 414 may be collinear with slit 1514, but this is not required. In one embodiment, two sets of collinear openings exist on opposite sides of inserts 1500, 1600. Inserts 1500, 1600 may include one or more slits 1514, and in embodiments with more than one slit 1514, the slits 1514 may have different sizes and positioning on inserts 1500, 1600, but similar sizes are preferred. In one embodiment, the different slits 1514 may be positioned such that the liquid level 610 is always positioned between the top and bottom of at least one slit 1514. The number and size of the slits 1514 may be driven by competing objectives of minimizing evaporation and providing adequate mixing. In practice, as Figure 15A and 16A As shown, a gradient-free or double-layered 1402 can exist in container 600 using inserts 1500 and 1600.

[0205] A first opening 414 and / or a second opening 416 may be located above slit 1514. Any opening above slit 1514 may facilitate ventilation. The number and size of openings above slit 1514 may be driven by competing objectives of providing adequate ventilation and minimizing evaporation. In some embodiments, the second opening 416 is preferred because it is less likely to become blocked (compared to the first opening 414). Blockage could interfere with ventilation and affect the liquid level 610 of the insert. Blockage may be more likely when using detergent-based reagents. The second opening 416 may not be necessary if blockage is not an issue. A chamfer (e.g., chamfer 424) around the second opening 416 is optional but can help prevent blockage of the second opening 416 by reducing the surface area used to form the film. The length of slit 1514 may be at least twice the diameter / height of the first opening 414 (all first openings 414 of inserts 1500, 1600 preferably have substantially the same size), and preferably up to 10 times the diameter / height of the first opening. The slit 1514 and the first opening 414 may have similar widths, but they may be different.

[0206] Inserts 1500 and 1600 may include all the benefits described herein with reference to insert 400, and may also include improved mixing capabilities relative to insert 400. That is, compared to a container 600 including insert 400 undergoing the same mixing process, a container 600 including insert 1500 or 1600, after undergoing the mixing process, contains a solution or suspension with improved homogeneity. Furthermore, the evaporation rate exhibited in a container 600 having inserts 1500 and 1600 may be similar to or close to the evaporation rate exhibited in a container 600 having insert 400.

[0207] method

[0208] Figure 13 The diagram illustrates a method 800 according to this disclosure. Method 800 may begin at step 802, wherein an insert 400 may be positioned inside a container 600. Inserts 1500 and 1600 may also be considered as alternatives when insert 400 is described with reference to method 800. Method 800 may proceed to step 804, wherein the container 600 is filled with a reagent. The order of steps 802 and 804 is expected to be interchangeable. Method 800 may optionally proceed to step 805, wherein the container 600 is sealed and shipped to, for example, a distributor or end user. Method 800 may then proceed to step 806, wherein the container 600 and insert 400 may be positioned on a container tray 110 (see reference). Figure 1The method 800 can then proceed to step 807, wherein the contents of one or more containers 600 in container tray 110 may be mixed and / or agitated by rotation, track movement, reversal, vibration and / or another suitable mixing mechanism as described above. After mixing, the concentration of the liquid or the distribution of solid support within the liquid is substantially the same inside and outside the insert 400. If uniform mixing cannot be achieved when the reagent contains a solute dissolved in the solution, for example, when the opening below the liquid surface is too small, or when there is not enough opening below the liquid surface, a suboptimal concentration of the solute may form within the insert 400 (e.g., too high or too low) due to evaporation of the liquid from inside the insert 400. The concentration of the solute within the insert 400 may be too low when the solute precipitates out of the solution due to disproportionate evaporation within the insert 400. In one embodiment, after loading the reagent into container 600, a first mixing scheme may include mixing for 30 seconds at 5 Hz, followed by mixing for 60 seconds at 3 Hz. Subsequent maintenance mixing can be performed at regular time intervals (e.g., every 30 minutes) and may include mixing the contents of container 600 at 5 Hz for 15 seconds, followed by mixing at 3 Hz for 30 seconds. The mixing scheme can be optimized to minimize the amount of mixing required to keep the particles suspended. Less mixing may result in a lower evaporation rate and a lower likelihood of bubble formation within insert 400, which could adversely affect level sensing. Alternative mixing methods are described in U.S. Patent No. 7,135,145.

[0209] Alternatively, the container 600 with the insert 400 may be positioned within the container tray 110 without containing any liquid. In this embodiment, the container 600 may be filled with reagent after it has been positioned within the container tray 110.

[0210] As used herein, "solid support" can refer to any solid substance or object of sufficient geometry to pass through the first opening 414 of the insert 400. A solid support may include any material that does not readily dissolve in a liquid medium containing it. Examples of solid support materials include metals, silica, glass, rubber, and plastics. In some embodiments, the solid support is formed of or comprises a magnetically responsive material. In other embodiments, the solid support may be adapted to incorporate an analyte of interest.

[0211] Method 800 may proceed to step 808, wherein a pipette tip 700 and an associated pipetting device (e.g., an automated pipette) may be inserted into container 600. Method 800 may then proceed to step 809, wherein level sensing may be performed to ensure that the pipette tip 700 has contacted the reagent within container 600. Once contact is confirmed, the pipette tip 700 and the associated pipetting device may retrieve a quantity of reagent from one of the containers 600. Each time an aliquot of reagent is retrieved, the pipette tip 700 may retrieve the reagent from container 600 at the same location. The retrieved reagent may be used for one or more tests or other analytical procedures performed by an automated analyzer. Analytical procedures may include any procedure for determining the presence of an analyte in a sample, including, for example, nucleic acid-based tests, immunoassays, chemical assays, etc.

[0212] After retrieving a certain amount of reagent, method 800 can proceed to optional steps ( Figure 13 (Not shown in the diagram), wherein it is determined whether the sensed liquid level in container 600 is above a minimum threshold liquid level (corresponding to the dead volume as described above). This determination can be made by any suitable mechanism, such as one or more liquid level sensing technologies, including capacitive level sensing and / or any of the technologies described in U.S. Patent No. 6,914,555. If the sensed liquid level is above the minimum threshold, then method 800 may return to step 808 to re-mix and / or agitate container 600. Returning to step 808 may resuspend particles precipitated from the suspension when mixing and agitation are stopped in step 810. If the sensed liquid level at step 812 is below the minimum threshold, then container 600 may be refilled with reagents or replaced with a new container 600.

[0213] Example 1

[0214] However, the following examples are intended to illustrate the contents of this disclosure and are not restrictive in nature. It should be understood that this disclosure covers additional examples that conform to the foregoing description.

[0215] A comparative study was conducted using a first container with a first insert having a circular opening and two enlarged square openings, a second container with a second insert having only a circular opening, and a third container without any inserts. The containers were substantially the same size, and the same amount of brine solution was supplied to each container. The first insert included a first row of openings having three circular openings (each with a diameter of 2.0 mm) spaced 16 mm apart from each other, and an enlarged square opening (3.8 mm wide) spaced 16 mm from the uppermost of the three circular openings. The outer perimeter of the square openings in the first row was defined by a thin section (0.25 mm thick) formed by four chamfered edges. Circular openings were formed in a 1.0 mm thick planar portion of the insert. The first insert included a second row of openings spaced apart on opposite sides of the first insert. The second row of openings included four circular openings (each with a diameter of 2.0 mm), each circular opening circumferentially aligned with one of the circular or square openings in the first row. The second row of openings also includes a square opening (3.8 mm wide) defined by a thin section (0.25 mm thick) spaced 13.0 mm from the topmost circular opening of the second row. The second insert includes two rows of opposing circular openings. Each of the two rows includes four circular openings. The positioning and spacing of the various openings in the second insert are the same as the positioning and spacing of the various openings in the first insert.

[0216] Using the first Panther During the first study conducted using the system (Hologic, Inc.; Marlborough, MA), a first container with a first insert having both a circular opening and an enlarged square opening experienced an evaporation rate of 18.0 μL / hr, a second container with a second insert having only a circular opening experienced an evaporation rate of 13.9 μL / hr, and a third container without any inserts experienced an evaporation rate of approximately 41.7 μL / hr. Using a second Panther... During the second study conducted by the system, the first container with a circular opening and an enlarged square opening experienced an evaporation rate of 17.2 μl / h, the second container with a second insert having only a circular opening experienced an evaporation rate of 14.3 μl / h, and the third container without any inserts experienced an evaporation rate of approximately 40.4 μl / h. For both studies, the test protocol / conditions were identical for each container, and all variables except for the inserts remained constant across the containers. Measurements were obtained once per day for each container over a seven-day period. The reported evaporation rates are the average of the seven measurements obtained over the seven-day period.

[0217] Comparative studies show that, in at least some embodiments, adding an enlarged opening (e.g., an enlarged square opening) to an insert containing only a circular opening of the same size can cause a suitable increase in the evaporation rate from the container having the insert. However, given the various benefits that can be provided by the enlarged square opening, a modest increase in the evaporation rate is acceptable, for example, to prevent or limit the formation of a vacuum within the container to achieve substantially uniform mixing that occurs both inside and outside the insert, and to improve the accuracy of level sensing.

[0218] Example 2

[0219] As in Example 1 above, the following examples are intended to be illustrative and not limiting of this disclosure. It should be understood that this disclosure covers additional embodiments consistent with the foregoing description.

[0220] In this example, a fourth container without inserts, a fifth container with a circular opening of similar size and two enlarged square openings (from the first insert in Example 1 above), and a sixth container with a fourth insert identical to the first insert but including an elongated slit replacing the circular opening at the corresponding position of the first insert are investigated. The fourth, fifth, and sixth containers all have similar dimensions. Unless otherwise stated, the first and fourth inserts also have similar dimensions. Each of the circular openings in the first and fourth inserts has a diameter of 2.0 mm. The slit has a width of 2.0 mm, with its bottom end positioned 38.0 mm from the bottom end of the third insert, and a length of 12.0 mm.

[0221] For this study, free HEX or ROX dye was manually added to the internal control reagent to obtain a final concentration of 0.3 μM. After adding the dye, 556 μL of the internal control was dispensed into each of three containers. Before dispensing the internal control reagent into the containers, 176 mL of sample processing reagent containing magnetically responsive particles was provided to each container. For the fourth container (without inserts), the internal control reagent was dispensed directly into the container, and for the fifth and sixth containers, the internal control reagent was dispensed into the containers via the first and fourth inserts, respectively, using a pipette. After adding the dye-containing internal control, each container was mixed using the same automated mixing protocol (e.g., the automated mixing protocol described in U.S. Patent No. 9,604,185). After mixing, 450 μL aliquots of each of the resulting mixtures were sequentially dispensed into five tubes in each of 24 integrally formed multi-tube units (MTUs). PCR vials for each corresponding tube were then prepared using 20 μL of oil and 30 μL of a mixture from the corresponding tube. Baseline fluorescence measurements were performed on each PCR vial using a thermal cycler.

[0222] The results of the study are Figure 17-19 As shown in the figure, Figure 17-19 Dot plots of fluorescence measurements obtained from PCR vials are shown. For each MTU, the Y-axis of these plots represents the ratio of the actual fluorescence measurement to the expected fluorescence measurement for each of the five PCR vials corresponding to that MTU. The expected fluorescence measurement is based on fluorescence readings from MTUs 13 through 24, where the reading of MTU 1 is compared to the reading of the corresponding tube for MTU 13, the reading of MTU 2 is compared to the reading of the corresponding tube for MTU 14, and so on. The X-axis of these plots represents the MTUs, where the order of the MTUs on the X-axis corresponds to the order in which the aliquots were obtained from the container, from the lowest to the highest MTU number.

[0223] As expected, Figure 17 The results showed essentially no variation among the different fluorescence measurements of the twelve MTUs prepared from the mixture in the fourth container (without inserts). Figure 18 The results clearly show the higher fluorescence measurements of the first few MTUs (especially the first MTU) prepared from the mixture in the fifth container (the insert without a slit), indicating the presence of a gradient within the first insert of the fifth container, where a higher concentration of the internal control is present near the liquid surface within the first insert. Figure 14 As shown in the diagram. In a homogeneous mixing vessel, the ratio of the calculated value to the estimated value should be approximately 1. Figure 19 As shown, the MTU prepared from the mixture in the sixth container (with the slit insert) showed essentially no change in fluorescence measurements, similar to that used in the fourth container. Figure 17 The measurements shown.

[0224] Example 3

[0225] As with Examples 1 and 2 above, the following examples are intended to illustrate, and not limit, this disclosure. It should be understood that this disclosure covers additional embodiments consistent with the foregoing description.

[0226] In this example, an investigation was conducted to compare the evaporation rate in a container including the first insert described in Examples 1 and 2 with the evaporation rate in a container including the fourth insert described in Example 2 above. Evaporation rates were determined using containers having either the first or fourth insert and containing the same sample preparation reagent in volumes of 176 mL, 122 mL, or 72 mL. The containers used in this example were of similar dimensions. After the sample preparation reagent was provided, the container was loaded into the Panther... The mixing turntable of the system is maintained at 32°C and 20% relative humidity for three to seven days.

[0227] like Figure 20As shown, the evaporation rates exhibited in containers with the first insert and the fourth insert, and the change in volume of the sample treatment reagent, showed no measurable difference. Therefore, although the fourth insert is shown to improve the homogeneity of liquids containing reagents that readily form gradients, adding a longitudinally oriented elongated slit to the insert does not adversely affect the evaporation rate from the corresponding container.

[0228] Each of the U.S. patent application publications and U.S. patents is incorporated herein by reference in its entirety.

[0229] It will be apparent to those skilled in the art that various modifications and variations can be made to the disclosed systems and processes without departing from the scope of this disclosure. Other embodiments of this disclosure will become apparent to those skilled in the art upon consideration of the description and practice of this disclosure herein. The specification and embodiments are intended to be illustrative only.

Claims

1. An insert for holding a liquid in a container, the insert comprising: The body includes a wall, an opening top end and an opening bottom end, and a tubular inner cavity extending from the opening top end to the opening bottom end; One or more first openings are formed in the wall, the first openings being located between the top end and the bottom end; and A first longitudinally oriented slit is formed through the wall, the first slit having a top end spatially separated from the top end of the body and a bottom end spatially separated from the bottom end of the body, such that the first slit is completely located between the top and bottom ends of the body and such that the top and bottom ends of the first slit are enclosed by the wall, the first slit having a length and a width, wherein the length of the first slit is at least twice the length or diameter of each of the first openings, and wherein the entire first slit is positioned closer to the top end than at least one of the first openings. The first slit is configured to allow liquid held in the container to enter the inner cavity of the body when the insert is secured inside the container.

2. The insert of claim 1, wherein the first slit is at least four times larger in length or diameter than each of the first openings.

3. The insert of claim 1, wherein the first slit is at least six times larger in length or diameter than each of the first openings.

4. The insert according to claim 1, wherein the first slit is disposed between at least two of the first openings and is collinear with at least two of the first openings.

5. The insert according to claim 1, wherein the length of the first slit is 6.0 times, 5.0 to 7.0 times, 3.0 to 10.0 times, or more than 3.0 times the width of the first slit.

6. The insert according to claim 1, wherein the length of the first slit is 12.0 mm, 11.5 mm to 12.5 mm, 10.0 mm to 15.0 mm, 5.0 mm to 20.0 mm, or more than 5.0 mm.

7. The insert according to claim 1, wherein the width of the first slit is equal to the width or diameter of at least one of the first openings.

8. The insert according to claim 7, wherein the width of the first slit is 1.0 mm to 4.0 mm, 1.0 mm to 3.0 mm, or 2.0 mm.

9. The insert according to claim 1, wherein each of the first openings is circular in shape.

10. The insert of claim 1, wherein the diameter of each of the first openings is 1.0 mm to 4.0 mm, 1.0 mm to 3.0 mm, or 2.0 mm.

11. The insert according to claim 1, wherein the diameter of each of the first openings is at least 2.0 mm.

12. The insert of claim 1, wherein the body tapers radially inward from the top end toward the bottom end.

13. The insert according to claim 1, wherein the inner diameter of the body is larger at the top end than the inner diameter of the body at the bottom end.

14. The insert according to claim 1, wherein at least one of the first openings is located below the midpoint of the body.

15. The insert of claim 1, wherein a majority of the first opening is located between the midpoint of the body and the bottom end.

16. The insert of claim 15, wherein two-thirds or more of the first opening is located between the midpoint of the body and the bottom end.

17. The insert of claim 1, further comprising at least one groove in the wall extending from the bottom end of the insert toward the top end.

18. The insert of claim 17, wherein the at least one slot comprises two opposing slots, each extending from the bottom end toward the top end.

19. The insert according to claim 17, wherein the at least one groove is a recess in the bottom end of the insert.

20. The insert of claim 1, wherein the body further comprises two or more resilient tabs at the tip of the insert, the tabs being configured to deflect radially inward when the insert is inserted into the container and resiliently pressed against the inner surface of the container.

21. The insert of claim 20, further comprising two or more additional slits extending from the top end toward the bottom end in the wall of the body, wherein each of the additional slits separates two of the two or more resilient tabs.

22. The insert of claim 21, wherein the body further includes one or more pawls at the tip of the insert, the one or more pawls being configured to engage with the inner surface of the container to secure the insert within the container.

23. The insert of claim 1, wherein the first opening comprises at least two first openings aligned axially in a first row on a first side of the body.

24. The insert of claim 23, wherein the first opening comprises at least two first openings axially aligned in a second row on a second side of the body, wherein the first row and the second row are opposite to each other on the body.

25. The insert of claim 24, wherein the first opening consists only of the first openings of the first row and the second row.

26. The insert of claim 25, wherein the first slit is collinear with the first opening of the first row or the first opening of the second row.

27. The insert of claim 1, wherein the body comprises one or more planar portions, and each of the first openings and the first slit are formed in the planar portion.

28. The insert of claim 1, further comprising a longitudinally oriented second slit, the longitudinally oriented second slit being circumferentially and longitudinally offset from the first slit.

29. The insert of claim 1, wherein the one or more first openings comprise a plurality of first openings.

30. The insert of claim 29, wherein the first slit is disposed closer to the top end than at least two of the plurality of first openings.

31. A system for limiting the evaporation of liquid from a container, comprising: A container that defines a volume partially filled with liquid, the container defining an opening at the top of the container and having a top surface at the bottom of the container; as well as An insert extending within the container according to any one of claims 2 to 27, wherein the top end of the body is adjacent to the top end of the container, and the bottom end of the body is adjacent to the top surface at the bottom end of the container.

32. The system of claim 31, wherein the surface of the liquid is disposed between the top and bottom ends of the first slit.

33. The system of claim 32, wherein the liquid contains a solid support.

34. The system of claim 33, wherein the solid support is a magnetically responsive particle or bead.

35. The system of claim 31, wherein the liquid is a combination liquid comprising a first liquid and a second liquid, the second liquid forming a gradient within the first liquid adjacent to the liquid surface within the insert.

36. A method for mixing contents within a container comprising an insert according to any one of claims 1 to 30, the container containing a first liquid, the method comprising: A second liquid is added to the container, thereby forming a combined liquid, the second liquid having a density lower than that of the first liquid, wherein after the second liquid is added to the first liquid, the surface of the combined liquid is disposed between the top and bottom ends of the first slit, and the gradient of the second liquid in the first liquid is disposed adjacent to the surface; as well as The combined liquids within the container are agitated, thereby mixing the first liquid and the second liquid within the inner cavity and outside the insert.

37. The method of claim 36, wherein agitating the combined liquid comprises moving the container about an orbital path.

38. The method of claim 37, wherein the track path is a circular track path.

39. The method of claim 36, further comprising extracting a certain amount of the combined liquid from the container after agitating the combined liquid.

40. The method of claim 39, further comprising, after extracting the amount of combined liquid from the container, agitating the container to promote mixing of the first liquid and the second liquid.

41. The method of claim 39, further comprising sensing the level of the combined liquid within the insert, comparing the sensed level to a threshold, and, when the sensed level of the combined liquid is below the threshold, refilling the container or replacing the container with additional amounts of each of the first liquid and the second liquid and additional amounts of the second liquid.

42. The method of claim 39, wherein the extraction of the amount of combined liquid from the container is performed using an automated pipette, and wherein the extraction comprises aspirating the amount of combined liquid.

43. The method of claim 42, wherein prior to extraction, the method further comprises capacitive or pressure-based level detection using the pipette to confirm that the pipette or the tip of the pipette fixed to the shaft of the pipette has contacted the combined liquid and at the position where extraction of the amount of the combined liquid begins.

Images