WO2020028406A1

WO2020028406A1 - Methods, devices, and apparatus for washing samples containing cells

Info

Publication number: WO2020028406A1
Application number: PCT/US2019/044205
Authority: WO
Inventors: Namyong Kim; Kong Leong CHENG; Ih Chin KON; Chyan Ying KE; Francis Lee
Original assignee: Curiox Biosystems Pte Ltd.
Priority date: 2018-07-30
Filing date: 2019-07-30
Publication date: 2020-02-06

Abstract

Methods, devices, and apparatus for washing samples containing cells are described. An apparatus includes one or more aspirators. A respective aspirator is configured to aspirate a liquid on the array plate. The respective aspirator includes a nozzle, and a tip of the nozzle is pointed in a non-vertical direction. A lid includes a cover plate having a first surface and a second surface. In some embodiments, a plurality of distinct and separate indentations defined on the second surface. In some embodiments, the second surface is flat. A device for at least partial insertion into a well includes a rod having a first end and a second end that is opposite to the first end; and one or more absorbers located adjacent to the first end of the rod. The one or more absorbers include a porous material.

Description

Methods, Devices, and Apparatus

for Washing Samples Containing Cells

TECHNICAL FIELD

[0001] The disclosed embodiments relate generally to methods, devices, and apparatus for washing samples (e g., cells, particles, etc.). More particularly, the disclosed embodiments relate to methods, devices, and apparatus for washing samples on array plates and slides.

BACKGROUND

[0002] An array plate is also called a microtiter plate, microplate, or microwell plate.

Array plates are typically used to hold respective liquid droplets separately for biological and/or chemical reaction. For example, a well-type array plate includes a plurality of wells so that each liquid droplet or each sample may be dispensed into a separate well for further processing. Typically, the number of wells is selected from 6, 24, 96, 384, 1536, 3456, and 9600.

[0003] Samples (e.g., cells) are frequently washed. Washing typically involves adding a wash solution to a sample solution, including samples (e.g., cells), on the slide and removing the mixture of the wash solution and the sample solution. By repeating the dilution and partial removal of the sample solution, the concentration of chemicals and/or biological reagents other than the samples are reduced. However, certain cells (e.g., suspension cells, non-adherent cells, and weakly adherent cells) do not strongly adhere to the slide. Thus, during removal of the mixture, cells may be removed along with the mixture, thereby reducing the number of cells that remain on the hydrophilic area of the slide after the washing. Because a reliability of cell- based reactions typically requires a sufficient number of cells, the loss of cells during washing negatively affects cell-based reactions.

[0004] In addition, variations in the sample washing increase measurement errors, which are not desirable for accurate assays.

SUMMARY

[0005] Accordingly, there is need for methods, devices, and apparatus that better retain cells during washing. Such methods, devices, and apparatus plates may replace the conventional methods, devices, and apparatus for washing cells. Such methods, devices, and apparatus reduce or eliminate the loss of cells during washing, thereby improving the reliability of cell-based reactions. Similarly, such methods, devices, and apparatus may be used in washing other types of samples, such as beads or particles conjugated with target molecules. In addition, such methods, devices, and apparatus improve the accuracy in assays and reduce the time required for washing samples.

[0006] A number of embodiments that overcome the limitations and disadvantages of existing methods, devices, and apparatus are presented in more detail below. These embodiments provide methods, devices, and apparatus for washing a sample in a solution.

[0007] As described in more detail below, in accordance with some embodiments, an apparatus for washing an array plate includes a plate mount for placing the array plate and one or more aspirators. A respective aspirator of the one or more aspirators is configured to aspirate a liquid on the array plate. The respective aspirator includes a nozzle, a tip of the nozzle pointed in a non-vertical direction.

[0008] In accordance with some embodiments, an apparatus for washing an array plate includes one or more aspirators. A respective aspirator of the one or more aspirators is configured to aspirate a liquid on an array plate. The apparatus also includes a plate mount rotatably coupled to a fulcrum, allowing the plate mount to tilt to: a first tilt position at a first time and a second tilt position at a second time that is distinct from the first time. The apparatus further includes a first set of one or more actuators coupled with the plate mount and configured to rotate the plate mount between the first tilt position and the second tilt position.

[0009] In accordance with some embodiments, a method for removing a liquid on an array plate includes obtaining an array plate with a liquid droplet thereon; placing at least a tip of a curved needle of an aspirator in the liquid droplet; and while at least the tip of the curved needle remains in the liquid droplet, aspirating at least a portion of the liquid droplet with the aspirator.

[0010] In accordance with some embodiments, a method for removing a liquid on an array plate includes obtaining an array plate with a liquid droplet thereon; tilting the array plate so that the array plate is in a non-horizontal position; and while the array plate is in the non horizontal position, aspirating at least a portion of the liquid droplet with an aspirator.

[0011] In accordance with some embodiments, a lid for use in washing of a sample on an array plate includes a cover plate having a first surface and a second surface that is opposite to the first surface, a plurality of distinct and separate indentations defined on the second surface.

[0012] In accordance with some embodiments, a combination of any first lid described herein and any second lid described herein is disclosed. The first lid and the second lid are configured to removably couple with each other. The second lid, at least when coupled with the first lid, is impermeable.

[0013] In accordance with some embodiments, a method includes obtaining an array plate; and placing any lid described herein.

[0014] In accordance with some embodiments, a lid for use on an array plate includes a cover plate having a first surface and a second surface that is opposite to the first surface. The second surface is configured to be placed toward the array plate and the second surface is flat.

[0015] In accordance with some embodiments, a combination of any lid described herein and any array plate described herein.

[0016] In accordance with some embodiments, a method includes obtaining an array plate; and, while a liquid droplet remains on the array plate, placing on the array plate a lid that includes a cover plate having a first surface and a second surface that is opposite to the first surface so that the second surface of the lid is placed toward the array plate. The second surface is flat.

[0017] In accordance with some embodiments, a device for at least partial insertion into a well includes a rod having a first end and a second end that is opposite to the first end; and one or more absorbers located adjacent to the first end of the rod. The one or more absorbers include a porous material.

[0018] In accordance with some embodiments, a method includes obtaining a well containing a solution; inserting the one or more absorbers of any device described herein at least partially into the well so that at least a portion of the solution is absorbed by the one or more absorbers; and, subsequent to inserting the one or more absorbers at least partially into the well, separating the one or more absorbers and the well so that the one or more absorbers cease to be placed at least partially in the well.

[0019] In accordance with some embodiments, a method includes obtaining an array plate defining a plurality of wells; concurrently inserting respective groups of one or more absorbers of any device described herein at least partially into respective wells of the plurality of wells so that at least a portion of a solution in a respective well is absorbed by a respective group of one or more absorbers; and subsequent to concurrently inserting the respective groups of one or more absorbers at least partially into the respective wells, separating the plate and the array plate.

[0020] In accordance with some embodiments, a device includes a plate having an array of hydrophilic areas; and one or more hydrophobic areas surrounding the array of hydrophilic. A respective hydrophilic area of the array of hydrophilic areas is indented from a surrounding hydrophobic area of the one or more hydrophobic areas. In some embodiments, the respective hydrophilic area includes at least two secondary areas and a primary area located between the two secondary areas, and the primary area is a rectangular area extending between the two secondary areas.

[0021] In some embodiments, the primary area is offset from the surrounding hydrophobic area by a first distance; and the two secondary areas are offset from the surrounding hydrophobic area by a second distance that is distinct from the first distance. In some embodiments, the primary area and the two secondary areas are offset from the surrounding hydrophobic area by a same distance. In some embodiments, the primary area has a rectangular area extending between the two secondary areas.

BRIEF DESCRIPTION OF THE DRAWINGS

[0022] For a better understanding of the aforementioned embodiments as well as additional embodiments, reference should be made to the Description of Embodiments below, in conjunction with the following drawings in which like reference numerals refer to corresponding parts throughout the figures.

[0023] Figures 1A-1C are perspective views of array plates in accordance with some embodiments.

[0024] Figures 1D-1F are partial plan views of example array plates in accordance with some embodiments.

[0025] Figures 1 G- 1H illustrate arrangement of dispensers and aspirators in accordance with some embodiments.

[0026] Figures 2A-2F are partial cross-sectional views of example array plates in accordance with some embodiments.

[0027] Figures 2G and 2H illustrate an example array plate in accordance with some embodiments.

[0028] Figures 3 A-3C illustrate a washer in accordance with some embodiments.

[0029] Figures 4A-4D illustrate a washer in accordance with some embodiments.

[0030] Figures 5A-5F illustrate an array plate in accordance with some embodiments.

[0031] Figures 5G-5K illustrate an array plate and a lid in accordance with some embodiments.

[0032] Figure 5L illustrates a combination of a first lid and a second lid in accordance with some embodiments. [0033] Figures 5M and 5N illustrate lids in accordance with some embodiments.

[0034] Figure 6A illustrates an array plate in accordance with some embodiments.

[0035] Figures 6B and 6C illustrate an array plate and a lid in accordance with some embodiments.

[0036] Figures 6D and 6E illustrate an array plate and a lid in accordance with some embodiments.

[0037] Figures 7A-7D illustrate a device for facilitating settling of cells and/or particles in accordance with some embodiments.

[0038] Figures 7E and 7F illustrate devices for facilitating settling of cells and/or particles in accordance with some embodiments.

[0039] Figures 8A-8C illustrate perspective views of array plates in accordance with some embodiments.

[0040] Figure 8D illustrates an example array plate in accordance with some embodiments.

[0041] Figure 8E illustrates numerical analysis results of flow over a rectangular hydrophobic area having respective depths in accordance with some embodiments.

[0042] Like reference numerals refer to corresponding parts throughout the drawings.

DESCRIPTION OF EMBODIMENTS

[0043] Methods, devices, and apparatus for washing samples are described. Reference will be made to certain embodiments, examples of which are illustrated in the accompanying drawings. While the claims will be described in conjunction with the embodiments, it will be understood that it is not intended to limit the claims to these particular embodiments alone. On the contrary, the embodiments are intended to cover alternatives, modifications and equivalents that are within the spirit and scope of the appended claims.

[0044] Moreover, in the following description, numerous specific details are set forth to provide a thorough understanding of the embodiments. However, it will be apparent to one of ordinary skill in the art that the embodiments may be practiced without these particular details. In other instances, methods, procedures, components, and networks that are well- known to those of ordinary skill in the art are not described in detail to avoid obscuring aspects of the embodiments.

[0045] It will also be understood that, although the terms first, second, etc. may be used herein to describe various elements, these elements should not be limited by these terms. These terms are only used to distinguish one element from another. For example, a first piston could be termed a second piston, and, similarly, a second piston could be termed a first piston, without departing from the scope of the embodiments. The first piston and the second piston are both pistons, but they are not the same piston.

[0046] The terminology used in the description of the embodiments herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used in the description of the embodiments and the appended claims, the singular forms“a,”“an,” and“the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will also be understood that the term“and/or” as used herein refers to and encompasses any and all possible combinations of one or more of the associated listed items. It will be further understood that the terms“comprises” and/or“comprising,” when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof.

[0047] As used herein, a liquid droplet refers to an aliquot of a liquid. A droplet may have any shape, and the term“droplet” is not used herein to describe a particular shape.

[0048] Figures 1 A-1C are perspective views of example array plates in accordance with some embodiments.

[0049] Figure 1A illustrates array plate 100 with base 120. On top of base 120, hydrophilic regions H2 (e.g., 112-1, 112-2, 112-3, 112-4, 112-5, 112-6, 112-7, and 112-8) are surrounded by hydrophobic area 110.

[0050] Figure 1B illustrates array plate 102, which is similar to array plate 100 except that hydrophilic regions 112 are offset from surrounding hydrophobic area 110 (e.g., hydrophilic region 112 is located below a plane defined by hydrophobic area 110).

[0051] In some embodiments, a respective hydrophilic region 112 (e.g., hydrophilic region 112 in Figure 1 A or Figure 1B) has a circular shape or an ellipsoidal shape.

[0052] Figure 1C illustrates array plate 104, which is similar to array plate 100 except that hydrophilic regions 112 (called herein“primary areas”) are coupled with one or more secondary areas, such as secondary areas 114 (e.g., 114-1) and 116 (e.g., 116-1). Although each hydrophilic region 112 in Figure 1C is coupled with two secondary areas, a respective hydrophilic region may have only one secondary area, or more than two secondary areas (e.g., three or four secondary areas). A secondary area is a hydrophilic region that is configured for placing a dispenser and/or an aspirator thereover. However, in some embodiments, a hydrophilic region without any secondary area (e.g., array plates 100 and 102 shown in Figures 1 A and 1B) is used, and a dispenser and an aspirator are positioned over the hydrophilic region (e.g., a primary area).

[0053] Figures 1D-1F are partial plan views of example array plates in accordance with some embodiments. In Figures 1D-1F, a respective hydrophilic region (or a primary area) has a circular shape, and a respective secondary area has a shape that corresponds to a portion of a circle (e.g., a crescent shape).

[0054] Figure 1D illustrates that a hydrophilic region (also called herein a primary area) and secondary areas are located on a same plane.

[0055] Figure 1E illustrates that a hydrophilic region (or a primary area) is located on a plane different from a plane on which secondary areas are located. Partial cross-sections of different embodiments that correspond to Figure 1E are illustrated in Figures 2A-2D.

[0056] Figure 1F illustrates a hydrophilic region (or a primary area) with four adjacent secondary areas in accordance with some embodiments.

[0057] Figures 1 G- 1H illustrate arrangement of dispensers and aspirators in accordance with some embodiments.

[0058] Figure 1G illustrates that a row of dispensers 180 and a row of aspirators 190 are used. As shown in Figure 1G, a row of dispensers 180 is used to dispense a wash liquid to a row of spots (or associated hydrophilic secondary areas) and a row of aspirators 190 is used to aspirate mixtures from the same row of spots (or associated hydrophilic secondary areas). In some cases, after a row of spots is washed, the array plate and/or the dispensers and the aspirators are moved so that the next row of spots can be washed.

[0059] Figure 1H illustrates that a two-dimensional array of dispensers 180 and a two- dimensional array of aspirators 190 are used.

[0060] Figure 2A illustrates a partial cross-section of array plate 220. Array plate 220 includes base 202 with secondary areas 214 and 216 located on a same plane as surrounding hydrophobic area 206. Primary area 212 is located offset from the plane on which secondary areas 214 and 216 are located (e.g., primary area 212 is indented so that primary area 212 is located deeper than secondary areas 214 and 216).

[0061] In some embodiments, the hydrophilic areas (e.g., the primary area and/or the secondary areas) include, or are made of, hydrophilic materials, such as polyvinyl alcohol, poly vinyl pyrrolidone, etc. In some embodiments, the hydrophobic area includes, or is made of, hydrophobic materials, such as a polytetrafluoroethylene (PTFE) matrix, polymethyl methacrylate), etc. [0062] In some embodiments, the hydrophilic areas (e.g., the primary area and/or the secondary areas) include, or are made of, glass (e.g., the primary area and/or the secondary areas are etched into glass). In some embodiments, the hydrophobic area includes a layer of hydrophobic material (e.g., a hydrophobic coating), such as a polytetrafluoroethylene (PTFE) layer (e.g., a PTFE tape). For example, the polytetrafluoroethylene (PTFE) matrix is patterned on a glass slide (e.g., a microscope slide) so that the PTFE matrix covers portions of the glass microscope slide and the remaining portions of the glass microscope slide are not covered by the PTFE matrix. The PTFE matrix has hydrophobic characteristics and the portions of the glass microscope slide that are not covered by the PTFE matrix have hydrophilic characteristics. Liquid droplet 208 (e.g., aqueous solutions) that include samples 204 (e.g., cells, particles, etc.) are typically placed on hydrophilic areas of the slide.

[0063] Figure 2B illustrates a partial cross-section of array plate 222. In array plate 222, secondary areas 214 and 216 are offset from the plane on which surrounding hydrophobic area 206 is located, and primary area 212 is offset from the plane on which secondary areas 214 and 216 are located (e.g., primary area 212 is located at a first depth that is offset from surrounding hydrophobic area 206, secondary areas 214 and 216 are located at a secondary depth that is offset from surrounding hydrophobic area 206, and the first depth is greater than the second depth).

[0064] Figure 2C illustrates a partial cross-section of array plate 224. In array plate 224, secondary areas 214 and 216 are located on a same plane as surrounding hydrophobic area 206. Primary area 212 is located offset from the plane on which secondary areas 214 and 216 are located (e.g., primary area 212 protrudes from secondary areas 214 and 216).

[0065] Figure 2D illustrates a partial cross-section of array plate 226. In array plate

226, secondary areas 214 and 216 are offset from the plane on which surrounding hydrophobic area 206 is located. Primary area 212 is offset from the plane on which secondary areas 214 and 216 are located (e.g., primary area 212 is located at a first depth from surrounding hydrophobic area 206, secondary areas 214 and 216 are located at a second depth that is offset from surrounding hydrophobic area 206, and the first depth is less than the second depth). In some embodiments, primary area 212 is located on a plane on which surrounding hydrophobic area 206 is located (e.g., the first depth is zero).

[0066] Figure 2E illustrates a partial cross-section of array plate 232. Array plate 232 is similar to array plate 222 shown in Figure 2B, except that region 242 around primary area 212 is filleted (e.g., edge(s) around primary area 212 has a rounded comer). In some embodiments, the region around primary area 212 (e.g., region 242) is chamfered (e.g., edge(s) around primary area 212 has a beveled corner). In some embodiments, the chamfered region is formed by removing material from array plate 232. In some embodiments, the chamfered region is formed by molding (e.g., injection molding).

[0067] Using array plate 232 with filleted or chamfered corners reduces cells remaining adjacent to the corners (after washing), thereby reduces trapping of one or more liquid droplets by the cells located adjacent to the corners (e.g., by capillary force between the cells and the plate surface around the comers). Thus, array plate 232 improves the efficiency of washing. In some cases, array plate 232 improves retention of cells so that more cells can be harvested for subsequent reading or detection. In some embodiments, a radius of curvature (of a rounded corner) is at least 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, or 1 mm. For example, the radius of curvature is 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, or 0.9 mm. In some embodiments, a chamfer width is at least 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, or 1 mm. For example, the chamfer width is 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, or 0.9 mm. In some embodiments, a chamfer depth is at least 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, or 1 mm. For example, the chamfer depth is 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, or 0.9 mm. In some embodiments, a chamfer length is at least 0.14 mm, 0.28 mm, 0.42 mm, 0.56 mm, 0.7 mm, or 1.4 mm. For example, the chamfer length is 0.7 mm, 0.84 mm, 0.98 mm, 1.12 mm, or 1.26 mm.

[0068] Figure 2F illustrates a partial cross-section of array plate 234. Array plate 234 is similar to array plate 232 shown in Figure 2E, except that regions 244 around secondary areas 214 and 216 are filleted (e.g., edges around second regions 214 and 216 have a rounded corner). In some embodiments, the regions around secondary areas 214 and 216 (e.g., regions 244) are chamfered (e.g., edges around secondary areas 214 and 216 have beveled corners). In some embodiments, the chamfered regions are formed by removing material from array plate 234. In some embodiments, the chamfered regions are formed by molding (e.g., injection molding).

[0069] Although Figures 2A-2F illustrate dispenser 180 and aspirator 190 to show the positioning of dispenser 180 over secondary area 214 and aspirator 190 over secondary area 216, dispenser 180 and aspirator 190 are not part of the array plate.

[0070] Figures 2G-2H illustrate an example array plate in accordance with some embodiments.

[0071] Figure 2G is a perspective view of a portion of the array plate in accordance with some embodiments. The portion of the array plate shown in Figure 2G has primary area 212 surrounded by region 242. In some embodiments, primary area 212 has a diameter of at least 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, or 10 mm. In some embodiments, primary area 212 has a diameter of at most 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, or 10 mm. In some embodiments, primary area 212 has a diameter between 1 mm and 5 mm, between 2 mm and 6 mm, between 3 mm and 7 mm, between 4 mm and 8 mm, between 5 mm and 9 mm, between 6 mm and 10 mm, between 7 mm and 11 mm, between 8 mm and 12 mm, between 9 mm and 13 mm, or between 10 mm and 14 mm. In some embodiments, primary area 212 has a diameter between 1 mm and 3 mm, between 2 mm and 4 mm, between 3 mm and 5 mm, between 4 mm and 6 mm, between 5 mm and 7 mm, between

6 mm and 8 mm, between 7 mm and 9 mm, between 8 mm and 10 mm, between 9 mm and 11 mm, or between 10 mm and 12 mm.

[0072] As explained above with respect to Figure 2E, in some embodiments, region

242 is filleted or chamfered. In some embodiments, region 242 is filleted and has a radius of curvature (Rl) that corresponds to at least 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 1.2 mm, 1.4 mm, 1.6 mm, 1.8 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, or 10 mm. In some embodiments, region 242 has a radius of curvature (Rl) that is less than 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 1.2 mm, 1.4 mm, 1.6 mm, 1.8 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm,

7 mm, 8 mm, 9 mm, or 10 mm. In some embodiments, the region 242 has a radius of curvature that is between 0.1 mm and 1 mm. In some embodiments, the region 242 has a radius of curvature that is between 0.2 mm and 0.8 mm.

[0073] The portion of the array plate shown in Figure 2G also has secondary areas 214 and 216. In Figure 2G, a respective second region (e.g., secondary area 214 or secondary area 216) is surrounded by region 244. In some embodiments, secondary area 214 or 216 has a length (along an axis extending from secondary area 214 to secondary area 216) of at least 1 mm, 2 mm, 3 mm, or 4 mm. In some embodiments, secondary area 214 or 216 has a length of at most 1 mm, 2 mm, 3 mm, or 4 mm. In some embodiments, secondary area 214 or 216 has a width of at least 1 mm, 2 mm, 3 mm, or 4 mm. In some embodiments, secondary area 214 or 216 has a width of at least 1 mm, 2 mm, 3 mm, or 4 mm.

[0074] In some embodiments, region 244 is filleted or chamfered. In some embodiments, region 244 is filleted and has a radius of curvature (R3) that corresponds to at least 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 1.2 mm, 1.4 mm, 1.6 mm, 1.8 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, or 10 mm. In some embodiments, region 244 has a radius of curvature (R3) that is less than 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 1.2 mm, 1.4 mm, 1.6 mm, 1.8 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, or 10 mm. In some embodiments, the region 244 has a radius of curvature that is between 0.1 mm and 1 mm. In some embodiments, the region 244 has a radius of curvature that is between 0.2 mm and 0.8 mm. In some embodiments, the radius of curvature (R3) of region 244 is less than the radius of curvature (Rl) of region 242.

[0075] Figure 2G also illustrates that an edge of secondary area 214 facing primary area

212 has a radius of curvature (R2) in some embodiments. In some embodiments, the radius of curvature (R2) corresponds to at least 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 1.2 mm, 1.4 mm, 1.6 mm, 1.8 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, or 10 mm. In some embodiments, the radius of curvature (R2) is less than 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 1.2 mm, 1.4 mm, 1.6 mm, 1.8 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, or 10 mm. In some embodiments, the radius of curvature (R2) is between 0.1 mm and 1 mm. In some embodiments, the radius of curvature (R2) is between 0.2 mm and 0.8 mm. In some embodiments, the radius of curvature (R2) is identical to the radius of curvature (Rl) of region 212. In some embodiments, the radius of curvature (R2) is identical to the radius of curvature (R3) of region 244.

[0076] In some embodiments, primary area 212 is indented, from an area (e.g., area

206 in Figure 2B) surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by at least 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 1.2 mm, 1.4 mm, 1.6 mm, 1.8 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, or 10 mm. For example, primary area 212 has a depth of at least 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 1.2 mm, 1.4 mm, 1.6 mm, 1.8 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, or 10 mm from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244).

[0077] In some embodiments, primary area 212 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by at most 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 1.2 mm, 1.4 mm, 1.6 mm, 1.8 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, or 10 mm. [0078] In some embodiments, primary area 212 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.1 mm and 0.2 mm, between 0.2 mm and 0.3 mm, between 0.3 mm and 0.4 mm, between 0.4 mm and 0.5 mm, between 0.5 mm and 0.6 mm, between 0.6 mm and 0.7 mm, between 0.7 mm and 0.8 mm, between 0.8 mm and 0.9 mm, between 0.9 mm and 1 mm, between 1 mm and 1.2 mm, between 1.2 mm and 1.4 mm, between 1.4 mm and 1.6 mm, between 1.6 mm and 1.8 mm, between 1.8 mm and 2 mm, between 2 mm and 3 mm, between 3 mm and 4 mm, between 4 mm and 5 mm, between 5 mm and 6 mm, between 6 mm and 7 mm, between 7 mm and 8 mm, between 8 mm and 9 mm, or between 9 mm and 10 mm. In some embodiments, primary area 212 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.1 mm and 1 mm, between 0.1 mm and 0.9 mm, between 0.1 mm and 0.8 mm, between 0.1 mm and 0.7 mm, between 0.1 mm and 0.6 mm, between 0.1 mm and 0.5 mm, between 0.1 mm and 0.4 mm, or between 0.1 mm and 0.3 mm. In some embodiments, primary area 212 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.09 mm and 1 mm, between 0.09 mm and 0.9 mm, between 0.09 mm and 0.8 mm, between 0.09 mm and 0.7 mm, between 0.09 mm and 0.6 mm, between 0.09 mm and 0.5 mm, between 0.09 mm and 0.4 mm, between 0.09 mm and 0.3 mm, between 0.09 mm and 0.2 mm, or between 0.09 mm and 0.1 mm. In some embodiments, primary area 212 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.08 mm and 1 mm, between 0.08 mm and 0.9 mm, between 0.08 mm and 0.8 mm, between 0.08 mm and 0.7 mm, between 0.08 mm and 0.6 mm, between 0.08 mm and

0.5 mm, between 0.08 mm and 0.4 mm, between 0.08 mm and 0.3 mm, between 0.08 mm and

0.2 mm, or between 0.08 mm and 0.1 mm. In some embodiments, primary area 212 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.07 mm and 1 mm, between 0.07 mm and 0.9 mm, between 0.07 mm and 0.8 mm, between 0.07 mm and 0.7 mm, between 0.07 mm and

0.6 mm, between 0.07 mm and 0.5 mm, between 0.07 mm and 0.4 mm, between 0.07 mm and

0.3 mm, between 0.07 mm and 0.2 mm, or between 0.07 mm and 0.1 mm. In some embodiments, primary area 212 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.06 mm and 1 mm, between 0.06 mm and 0.9 mm, between 0.06 mm and 0.8 mm, between 0.06 mm and 0.7 mm, between 0.06 mm and 0.6 mm, between 0.06 mm and 0.5 mm, between 0.06 mm and 0.4 mm, between 0.06 mm and 0.3 mm, between 0.06 mm and 0.2 mm, or between 0.06 mm and 0.1 mm. In some embodiments, primary area 212 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.05 mm and 1 mm, between 0.05 mm and 0.9 mm, between 0.05 mm and 0.8 mm, between 0.05 mm and 0.7 mm, between 0.05 mm and 0.6 mm, between 0.05 mm and 0.5 mm, between 0.05 mm and 0.4 mm, between 0.05 mm and 0.3 mm, between 0.05 mm and 0.2 mm, or between 0.05 mm and 0.1 mm. In some embodiments, primary area 212 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.04 mm and 1 mm, between 0.04 mm and 0.9 mm, between 0.04 mm and 0.8 mm, between 0.04 mm and 0.7 mm, between 0.04 mm and 0.6 mm, between 0.04 mm and 0.5 mm, between 0.04 mm and 0.4 mm, between 0.04 mm and 0.3 mm, between 0.04 mm and 0.2 mm, or between 0.04 mm and 0.1 mm. In some embodiments, primary area 212 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.03 mm and 1 mm, between 0.03 mm and 0.9 mm, between 0.03 mm and 0.8 mm, between 0.03 mm and 0.7 mm, between 0.03 mm and 0.6 mm, between 0.03 mm and 0.5 mm, between 0.03 mm and 0.4 mm, between 0.03 mm and 0.3 mm, between 0.03 mm and 0.2 mm, or between 0.03 mm and 0.1 mm. In some embodiments, primary area 212 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.02 mm and 1 mm, between 0.02 mm and 0.9 mm, between 0.02 mm and 0.8 mm, between 0.02 mm and 0.7 mm, between 0.02 mm and 0.6 mm, between 0.02 mm and 0.5 mm, between 0.02 mm and 0.4 mm, between 0.02 mm and 0.3 mm, between 0.02 mm and 0.2 mm, or between 0.02 mm and 0.1 mm. In some embodiments, primary area 212 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.01 mm and 1 mm, between 0.01 mm and 0.9 mm, between 0.01 mm and 0.8 mm, between 0.01 mm and 0.7 mm, between 0.01 mm and 0.6 mm, between 0.01 mm and 0.5 mm, between 0.01 mm and 0.4 mm, between 0.01 mm and 0.3 mm, between 0.01 mm and 0.2 mm, or between 0.01 mm and 0.1 mm.

[0079] In some embodiments, primary area 212 is indented, from the area (e.g., area

206 in Figure 2B) surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by at least 0.1 % of the diameter of primary area 212, 0.2 % of the diameter of primary area 212, 0.3 % of the diameter of primary area 212, 0.4 % of the diameter of primary area 212, 0.5 % of the diameter of primary area 212, 0.6 % of the diameter of primary area 212, 0.7 % of the diameter of primary area 212, 0.8 % of the diameter of primary area 212, 0.9 % of the diameter of primary area 212, 1 % of the diameter of primary area 212, 1.2 % of the diameter of primary area 212, 1.4 % of the diameter of primary area 212, 1.6 % of the diameter of primary area 212, 1.8 % of the diameter of primary area 212, 2 % of the diameter of primary area 212, 3 % of the diameter of primary area 212, 4 % of the diameter of primary area 212, 5 % of the diameter of primary area 212, 6 % of the diameter of primary area 212, 7 % of the diameter of primary area 212, 8 % of the diameter of primary area 212, 9 % of the diameter of primary area 212, 10 % of the diameter of primary area 212, 20 % of the diameter of primary area 212, 30 % of the diameter of primary area 212, 40 % of the diameter of primary area 212, 50 % of the diameter of primary area 212, 60 % of the diameter of primary area 212, or 70 % of the diameter of primary area 212.

[0080] In some embodiments, primary area 212 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by at most 0.1 % of the diameter of primary area 212, 0.2 % of the diameter of primary area 212, 0.3 % of the diameter of primary area 212, 0.4 % of the diameter of primary area 212, 0.5 % of the diameter of primary area 212, 0.6 % of the diameter of primary area 212, 0.7 % of the diameter of primary area 212, 0.8 % of the diameter of primary area 212, 0.9 % of the diameter of primary area 212, 1 % of the diameter of primary area 212, 1.2 % of the diameter of primary area 212, 1.4 % of the diameter of primary area 212, 1.6 % of the diameter of primary area 212, 1.8 % of the diameter of primary area 212, 2 % of the diameter of primary area 212, 3 % of the diameter of primary area 212, 4 % of the diameter of primary area 212, 5 % of the diameter of primary area 212, 6 % of the diameter of primary area 212, 7 % of the diameter of primary area 212, 8 % of the diameter of primary area 212, 9 % of the diameter of primary area 212, 10 % of the diameter of primary area 212, 20 % of the diameter of primary area 212, 30 % of the diameter of primary area 212, 40 % of the diameter of primary area 212, 50 % of the diameter of primary area 212, 60 % of the diameter of primary area 212, or 70 % of the diameter of primary area 212.

[0081] In some embodiments, primary area 212 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 1 % of the diameter of primary area 212 and 2 % of the diameter of primary area 212, between 2 % of the diameter of primary area 212 and 3 % of the diameter of primary area 212, between 3 % of the diameter of primary area 212 and 4 % of the diameter of primary area 212, between 4 % of the diameter of primary area 212 and 5 % of the diameter of primary area 212, between 5 % of the diameter of primary area 212 and 6 % of the diameter of primary area 212, between 6 % of the diameter of primary area 212 and 7 % of the diameter of primary area 212, between 7 % of the diameter of primary area 212 and 8 % of the diameter of primary area 212, between 8 % of the diameter of primary area 212 and 9 % of the diameter of primary area 212, between 9 % of the diameter of primary area 212 and 10 % of the diameter of primary area 212, between 10 % of the diameter of primary area 212 and 12 % of the diameter of primary area 212, between 12 % of the diameter of primary area 212 and 14 % of the diameter of primary area 212, between 14 % of the diameter of primary area 212 and 16 % of the diameter of primary area 212, between 16 % of the diameter of primary area 212 and 18 % of the diameter of primary area 212, between 18 % of the diameter of primary area 212 and 20 % of the diameter of primary area 212, between 20 % of the diameter of primary area 212 and 30 % of the diameter of primary area 212, between 30 % of the diameter of primary area 212 and 40 % of the diameter of primary area 212, between 40 % of the diameter of primary area 212 and 50 % of the diameter of primary area 212, between 50 % of the diameter of primary area 212 and 60 % of the diameter of primary area 212, or between 60 % of the diameter of primary area 212 and 70 % of the diameter of primary area 212. In some embodiments, primary area 212 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 1 % of the diameter of primary area 212 and 10 % of the diameter of primary area 212, between 1 % of the diameter of primary area 212 and 9 % of the diameter of primary area 212, between 1 % of the diameter of primary area 212 and 8 % of the diameter of primary area 212, between 1 % of the diameter of primary area 212 and 7 % of the diameter of primary area 212, between 1 % of the diameter of primary area 212 and 6 % of the diameter of primary area 212, between 1 % of the diameter of primary area 212 and 5 % of the diameter of primary area 212, between 1 % of the diameter of primary area 212 and 4 % of the diameter of primary area 212, or between 1 % of the diameter of primary area 212 and 3 % of the diameter of primary area 212. In some embodiments, primary area 212 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.9 % of the diameter of primary area 212 and 10 % of the diameter of primary area 212, between 0.9 % of the diameter of primary area 212 and 9 % of the diameter of primary area 212, between 0.9 % of the diameter of primary area 212 and 8 % of the diameter of primary area 212, between 0.9 % of the diameter of primary area 212 and 7 % of the diameter of primary area 212, between 0.9 % of the diameter of primary area 212 and 6 % of the diameter of primary area 212, between 0.9 % of the diameter of primary area 212 and 5 % of the diameter of primary area 212, between 0.9 % of the diameter of primary area 212 and 4 % of the diameter of primary area 212, between 0.9 % of the diameter of primary area 212 and 3 % of the diameter of primary area 212, between 0.9 % of the diameter of primary area 212 and 2 % of the diameter of primary area 212, or between 0.9 % of the diameter of primary area 212 and 1 % of the diameter of primary area 212. In some embodiments, primary area 212 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.8 % of the diameter of primary area 212 and 10 % of the diameter of primary area 212, between 0.8 % of the diameter of primary area 212 and 9 % of the diameter of primary area 212, between 0.8 % of the diameter of primary area 212 and 8 % of the diameter of primary area 212, between 0.8 % of the diameter of primary area 212 and 7 % of the diameter of primary area 212, between 0.8 % of the diameter of primary area 212 and 6 % of the diameter of primary area 212, between 0.8 % of the diameter of primary area 212 and 5 % of the diameter of primary area 212, between 0.8 % of the diameter of primary area 212 and 4 % of the diameter of primary area 212, between 0.8 % of the diameter of primary area 212 and 3 % of the diameter of primary area 212, between 0.8 % of the diameter of primary area 212 and 2 % of the diameter of primary area 212, or between 0.8 % of the diameter of primary area 212 and 1 % of the diameter of primary area 212. In some embodiments, primary area 212 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.7 % of the diameter of primary area 212 and 10 % of the diameter of primary area 212, between 0.7 % of the diameter of primary area 212 and 9 % of the diameter of primary area 212, between 0.7 % of the diameter of primary area 212 and 8 % of the diameter of primary area 212, between 0.7 % of the diameter of primary area 212 and 7 % of the diameter of primary area 212, between 0.7 % of the diameter of primary area 212 and 6 % of the diameter of primary area 212, between 0.7 % of the diameter of primary area 212 and 5 % of the diameter of primary area 212, between 0.7 % of the diameter of primary area 212 and 4 % of the diameter of primary area 212, between 0.7 % of the diameter of primary area 212 and 3 % of the diameter of primary area 212, between 0.7 % of the diameter of primary area 212 and 2 % of the diameter of primary area 212, or between 0.7 % of the diameter of primary area 212 and 1 % of the diameter of primary area 212. In some embodiments, primary area 212 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.6 % of the diameter of primary area 212 and 10 % of the diameter of primary area 212, between 0.6 % of the diameter of primary area 212 and 9 % of the diameter of primary area 212, between 0.6 % of the diameter of primary area 212 and 8 % of the diameter of primary area 212, between 0.6 % of the diameter of primary area 212 and 7 % of the diameter of primary area 212, between 0.6 % of the diameter of primary area 212 and 6 % of the diameter of primary area 212, between 0.6 % of the diameter of primary area 212 and 5 % of the diameter of primary area 212, between 0.6 % of the diameter of primary area 212 and 4 % of the diameter of primary area 212, between 0.6 % of the diameter of primary area 212 and 3 % of the diameter of primary area 212, between 0.6 % of the diameter of primary area 212 and 2 % of the diameter of primary area 212, or between 0.6 % of the diameter of primary area 212 and 1 % of the diameter of primary area 212. In some embodiments, primary area 212 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.5 % of the diameter of primary area 212 and 10 % of the diameter of primary area 212, between 0.5 % of the diameter of primary area 212 and 9 % of the diameter of primary area 212, between 0.5 % of the diameter of primary area 212 and 8 % of the diameter of primary area 212, between 0.5 % of the diameter of primary area 212 and 7 % of the diameter of primary area 212, between 0.5 % of the diameter of primary area 212 and 6 % of the diameter of primary area 212, between 0.5 % of the diameter of primary area 212 and 5 % of the diameter of primary area 212, between 0.5 % of the diameter of primary area 212 and 4 % of the diameter of primary area 212, between 0.5 % of the diameter of primary area 212 and 3 % of the diameter of primary area 212, between 0.5 % of the diameter of primary area 212 and 2 % of the diameter of primary area 212, or between 0.5 % of the diameter of primary area 212 and 1 % of the diameter of primary area 212. In some embodiments, primary area 212 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.4 % of the diameter of primary area 212 and 10 % of the diameter of primary area 212, between 0.4 % of the diameter of primary area 212 and 9 % of the diameter of primary area 212, between 0.4 % of the diameter of primary area 212 and 8 % of the diameter of primary area 212, between 0.4 % of the diameter of primary area 212 and 7 % of the diameter of primary area 212, between 0.4 % of the diameter of primary area 212 and 6 % of the diameter of primary area 212, between 0.4 % of the diameter of primary area 212 and 5 % of the diameter of primary area 212, between 0.4 % of the diameter of primary area 212 and 4 % of the diameter of primary area 212, between 0.4 % of the diameter of primary area 212 and 3 % of the diameter of primary area 212, between 0.4 % of the diameter of primary area 212 and 2 % of the diameter of primary area 212, or between 0.4 % of the diameter of primary area 212 and 1 % of the diameter of primary area 212. In some embodiments, primary area 212 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.3 % of the diameter of primary area 212 and 10 % of the diameter of primary area 212, between 0.3 % of the diameter of primary area 212 and 9 % of the diameter of primary area 212, between 0.3 % of the diameter of primary area 212 and 8 % of the diameter of primary area 212, between 0.3 % of the diameter of primary area 212 and 7 % of the diameter of primary area 212, between 0.3 % of the diameter of primary area 212 and 6 % of the diameter of primary area 212, between 0.3 % of the diameter of primary area 212 and 5 % of the diameter of primary area 212, between 0.3 % of the diameter of primary area 212 and 4 % of the diameter of primary area 212, between 0.3 % of the diameter of primary area 212 and 3 % of the diameter of primary area 212, between 0.3 % of the diameter of primary area 212 and 2 % of the diameter of primary area 212, or between 0.3 % of the diameter of primary area 212 and 1 % of the diameter of primary area 212. In some embodiments, primary area 212 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.2 % of the diameter of primary area 212 and 10 % of the diameter of primary area 212, between 0.2 % of the diameter of primary area 212 and 9 % of the diameter of primary area 212, between 0.2 % of the diameter of primary area 212 and 8 % of the diameter of primary area 212, between 0.2 % of the diameter of primary area 212 and 7 % of the diameter of primary area 212, between 0.2 % of the diameter of primary area 212 and 6 % of the diameter of primary area 212, between 0.2 % of the diameter of primary area 212 and 5 % of the diameter of primary area 212, between 0.2 % of the diameter of primary area 212 and 4 % of the diameter of primary area 212, between 0.2 % of the diameter of primary area 212 and 3 % of the diameter of primary area 212, between 0.2 % of the diameter of primary area 212 and 2 % of the diameter of primary area 212, or between 0.2 % of the diameter of primary area 212 and 1 % of the diameter of primary area 212. In some embodiments, primary area 212 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.1 % of the diameter of primary area 212 and 10 % of the diameter of primary area 212, between 0.1 % of the diameter of primary area 212 and 9 % of the diameter of primary area 212, between 0.1 % of the diameter of primary area 212 and 8 % of the diameter of primary area 212, between 0.1 % of the diameter of primary area 212 and 7 % of the diameter of primary area 212, between 0.1 % of the diameter of primary area 212 and 6 % of the diameter of primary area 212, between 0.1 % of the diameter of primary area 212 and 5 % of the diameter of primary area 212, between 0.1 % of the diameter of primary area 212 and 4 % of the diameter of primary area 212, between 0.1 % of the diameter of primary area 212 and 3 % of the diameter of primary area 212, between 0.1 % of the diameter of primary area 212 and 2 % of the diameter of primary area 212, or between 0.1 % of the diameter of primary area 212 and 1 % of the diameter of primary area 212.

[0082] In some embodiments, at least one of secondary areas 214 and 216 is indented, from an area (e.g., area 206 in Figure 2B) surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by at least 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 1.2 mm, 1.4 mm, 1.6 mm, 1.8 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, or 10 mm. In some embodiments, secondary area 214 is indented from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by a first depth and secondary area 216 is indented from the area surrounding primary area 212 and secondary areas 214 and 216, by a second depth that is distinct from the first depth. In some embodiments, secondary areas 214 and 216 are indented from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244) by a same depth. For example, in some embodiments, both secondary areas 214 and 216 are indented, from the area (e.g., area 206 in Figure 2B) surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by at least 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 1.2 mm, 1.4 mm, 1.6 mm, 1.8 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, or 10 mm.

[0083] In some embodiments, at least one of secondary areas 214 and 216 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by at most 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 1.2 mm, 1.4 mm, 1.6 mm, 1.8 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, or 10 mm. For example, in some embodiments, both secondary areas 214 and 216 are indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by at most 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 1.2 mm, 1.4 mm, 1.6 mm, 1.8 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, or 10 mm. [0084] In some embodiments, at least one of secondary areas 214 and 216 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.1 mm and 0.2 mm, between 0.2 mm and 0.3 mm, between 0.3 mm and 0.4 mm, between 0.4 mm and 0.5 mm, between 0.5 mm and 0.6 mm, between 0.6 mm and 0.7 mm, between 0.7 mm and 0.8 mm, between 0.8 mm and 0.9 mm, between 0.9 mm and 1 mm, between 1 mm and 1.2 mm, between 1.2 mm and 1.4 mm, between 1.4 mm and 1.6 mm, between 1.6 mm and 1.8 mm, between 1.8 mm and 2 mm, between 2 mm and 3 mm, between 3 mm and 4 mm, between 4 mm and 5 mm, between 5 mm and 6 mm, between 6 mm and 7 mm, between 7 mm and 8 mm, between 8 mm and 9 mm, or between 9 mm and 10 mm. In some embodiments, at least one of secondary areas 214 and 216 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.1 mm and 1 mm, between 0.1 mm and 0.9 mm, between 0.1 mm and 0.8 mm, between 0.1 mm and 0.7 mm, between 0.1 mm and 0.6 mm, between 0.1 mm and 0.5 mm, between 0.1 mm and 0.4 mm, or between 0.1 mm and 0.3 mm. In some embodiments, at least one of secondary areas 214 and 216 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.09 mm and 1 mm, between 0.09 mm and 0.9 mm, between 0.09 mm and 0.8 mm, between 0.09 mm and 0.7 mm, between 0.09 mm and 0.6 mm, between 0.09 mm and 0.5 mm, between 0.09 mm and 0.4 mm, between 0.09 mm and 0.3 mm, between 0.09 mm and 0.2 mm, or between 0.09 mm and 0.1 mm. In some embodiments, at least one of secondary areas 214 and 216 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.08 mm and 1 mm, between 0.08 mm and 0.9 mm, between 0.08 mm and 0.8 mm, between 0.08 mm and 0.7 mm, between 0.08 mm and 0.6 mm, between 0.08 mm and 0.5 mm, between 0.08 mm and 0.4 mm, between 0.08 mm and 0.3 mm, between 0.08 mm and 0.2 mm, or between 0.08 mm and 0.1 mm. In some embodiments, at least one of secondary areas 214 and 216 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.07 mm and 1 mm, between 0.07 mm and 0.9 mm, between 0.07 mm and 0.8 mm, between 0.07 mm and 0.7 mm, between 0.07 mm and 0.6 mm, between 0.07 mm and 0.5 mm, between 0.07 mm and 0.4 mm, between 0.07 mm and 0.3 mm, between 0.07 mm and 0.2 mm, or between 0.07 mm and 0.1 mm. In some embodiments, at least one of secondary areas 214 and 216 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.06 mm and 1 mm, between 0.06 mm and 0.9 mm, between 0.06 mm and 0.8 mm, between 0.06 mm and 0.7 mm, between 0.06 mm and 0.6 mm, between 0.06 mm and 0.5 mm, between 0.06 mm and 0.4 mm, between 0.06 mm and 0.3 mm, between 0.06 mm and 0.2 mm, or between 0.06 mm and 0.1 mm. In some embodiments, at least one of secondary areas 214 and 216 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.05 mm and 1 mm, between 0.05 mm and 0.9 mm, between 0.05 mm and 0.8 mm, between 0.05 mm and 0.7 mm, between 0.05 mm and 0.6 mm, between 0.05 mm and 0.5 mm, between 0.05 mm and 0.4 mm, between 0.05 mm and 0.3 mm, between 0.05 mm and 0.2 mm, or between 0.05 mm and 0.1 mm. In some embodiments, at least one of secondary areas 214 and 216 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.04 mm and 1 mm, between 0.04 mm and 0.9 mm, between 0.04 mm and 0.8 mm, between 0.04 mm and 0.7 mm, between 0.04 mm and 0.6 mm, between 0.04 mm and 0.5 mm, between 0.04 mm and 0.4 mm, between 0.04 mm and 0.3 mm, between 0.04 mm and 0.2 mm, or between 0.04 mm and 0.1 mm. In some embodiments, at least one of secondary areas 214 and 216 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.03 mm and 1 mm, between 0.03 mm and 0.9 mm, between 0.03 mm and 0.8 mm, between 0.03 mm and 0.7 mm, between 0.03 mm and 0.6 mm, between 0.03 mm and 0.5 mm, between 0.03 mm and 0.4 mm, between 0.03 mm and 0.3 mm, between 0.03 mm and 0.2 mm, or between 0.03 mm and 0.1 mm. In some embodiments, at least one of secondary areas 214 and 216 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.02 mm and 1 mm, between 0.02 mm and 0.9 mm, between 0.02 mm and 0.8 mm, between 0.02 mm and 0.7 mm, between 0.02 mm and 0.6 mm, between 0.02 mm and 0.5 mm, between 0.02 mm and 0.4 mm, between 0.02 mm and 0.3 mm, between 0.02 mm and 0.2 mm, or between 0.02 mm and 0.1 mm. In some embodiments, at least one of secondary areas 214 and 216 is indented, from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244), by between 0.01 mm and 1 mm, between 0.01 mm and 0.9 mm, between 0.01 mm and 0.8 mm, between 0.01 mm and 0.7 mm, between 0.01 mm and 0.6 mm, between 0.01 mm and 0.5 mm, between 0.01 mm and 0.4 mm, between 0.01 mm and 0.3 mm, between 0.01 mm and 0.2 mm, or between 0.01 mm and 0.1 mm . [0085] In some embodiments, primary area 212 and secondary areas 214 and 216 are indented from the area surrounding primary area 212 and secondary areas 214 and 216 (and chamfered or filleted regions, such as region 244) by a same depth.

[0086] Figure 2H is a partial cross-sectional view of the array plate shown in Figure

2G. Although Figure 2G shows a portion of the array plate that includes single primary area 212, the array plate may have a plurality of primary areas (e.g., in a manner analogous to array plates shown in Figures 1 A-1C). The partial cross-sectional view shown in Figure 2H includes two primary areas and surrounding features (e.g., secondary areas).

[0087] The array plate shown in Figures 2G-2H have rounded corners for both primary and secondary areas, which further improves the efficiency of washing operations. In some cases, the array plate with rounded corners for both primary and secondary areas also improves retention of cells, which, in turn, increases the number of cells that can be collected for subsequent analysis (e.g., optical reading, chemical analysis, etc.).

[0088] Figures 3 A-3C illustrate a washer 302 in accordance with some embodiments.

[0089] In Figure 3A, the washer 302 includes a plate mount 304 for placing an array plate (e.g., array plate 232) thereon. The washer 302 also includes one or more aspirators (e.g., aspirator 310). A respective aspirator (e.g., aspirator 310) is configured to aspirate a liquid on the array plate. The respective aspirator includes a nozzle 312, a tip of which is pointed in a non-vertical direction (e.g., in a horizontal direction). In some embodiments, the tip of the nozzle is pointed in a direction that forms an angle that is at least 45 degrees with respect to a surface normal of a secondary area (e.g., area 216). For example, the tip of the nozzle is pointed in a direction that forms at least 60 degrees with respect to the surface normal of the secondary area. In another example, the tip of the nozzle is pointed in a direction that forms 90 degrees with respect to the surface normal of the secondary area (e.g., the tip of the nozzle is oriented horizontally).

[0090] In some embodiments, as shown in Figure 3A, the tip of the nozzle is pointed away from primary region 212. In some embodiments, the tip of the nozzle is pointed toward primary region 212.

[0091] In some embodiments, the tip of the nozzle includes a needle (e.g., needle 314 in Figure 3B). In some embodiments, the needle is a curved needle. In some embodiments, the tip of the curved needle pointing away from the primary region 212. [0092] In some embodiments, the needle is a straight needle (e.g., needle 316 in Figure

3C). In some embodiments, the needle is mounted at an angle or the aspirator is mounted at an angle so that the tip of the straight needle is pointing away from the primary region 212.

[0093] Figures 4A-4D illustrate a washer 402 in accordance with some embodiments.

[0094] In Figure 4A, the washer 402 includes one or more aspirators 190 and a plate mount 404. The plate mount 404 is rotatably coupled to a fulcrum 406. In some embodiments, the plate mount 404 is coupled to a shaft through a bearing (e.g., a wheel bearing), so that the plate mount 404 can rotate relative to the shaft.

[0095] In Figure 4A, the washer 402 also includes an actuator 408 coupled to the plate mount 404 for moving the plate mount 404 (e.g., rotating the plate mount 404 around the fulcrum 406). In some embodiments, the actuator 408 includes a linear actuator (e.g., a linear motor, a rack-and-pinion mechanism, etc.). When the actuator 408 includes a linear actuator, in some cases, the actuator 408 is slidingly (and optionally, rotationally) coupled with the plate mount 404. In some embodiments, the actuator 408 includes a rotational actuator (e.g., a stepper motor, a direct current motor, etc.) that is coupled to the plate mount 404 for rotating the plate mount 404.

[0096] In some embodiments, the washer 402 includes one or more dispensers 180 for providing a wash solution to a respective primary area (e.g., by dispensing the wash solution to a secondary area, such as secondary area 214). In some embodiments, the dispenser 180 is coupled with one or more actuators configured for moving the dispenser 180 (e.g., for lateral and/or vertical positioning).

[0097] In some embodiments, the aspirator 190 is coupled with one or more actuators

192 configured for moving the aspirator 190 (e.g., for lateral and/or vertical positioning). In some embodiments, the washer 402 includes one or more processors 410 (e.g., one or more microprocessors) communicatively coupled with one or more of: the actuator 192 and the actuator 408.

[0098] Figure 4B illustrates that the dispenser 180 has been moved away from the array plate 232 (e.g., by one or more actuators coupled with the dispenser 180).

[0099] Figure 4C illustrates that the actuator 408 has tilted the plate mount 404 (e.g., the actuator 408 has rotated the plate mount 404 with respect to the fulcrum 406).

[00100] Figure 4D illustrates that the actuator 192 has moved the aspirator 190 in proximity to the array plate 232 on the plate mount 404 so that at least a portion of the aspirator 190 (e.g., a tip of the aspirator 190) is in the liquid droplet 208. [00101] Removing (or aspirating) at least a portion of the liquid 208 while the plate mount 404 (and the array plate 232) is tilted facilitates removing of the liquid 208. For example, the residual volume of the liquid 208 is reduced by removing the liquid 208 while the plate mount 404 is tilted.

[00102] In some embodiments, the washers shown in Figures 3 A-3C and 4A-4D include additional components not shown in these figures. For example, the washers shown in Figures 3A-3C and 4A-4D include one or more pumps (for aspiration), one or more liquid reservoirs (for dispensing, for example, a wash solution), and one or more agitators (for mixing and/or agitating respective solutions on corresponding primary areas). For brevity, such components are not described herein.

[00103] Figures 5A-5F illustrate an array plate in accordance with some embodiments.

[00104] Figure 5A shows example array plate 502 having two primary areas 112 (e.g., primary areas 112-1 and 112-2). In some embodiments, a surface 110 surrounding the two primary areas 112 is a hydrophobic area.

[00105] Figures 5B-5F show isometric cross-sectional views of array plate 502 shown in Figure 5A.

[00106] Figure 5B illustrates that liquid droplets 208-1 and 208-2 are placed on primary areas 112. In some cases, a volume of the liquid droplet ranges from 1 pl to 80 mΐ (for a well with a primary area having 6 mm diameter and a depth of 0.7 mm from the hydrophobic surface). In some cases, a volume of the liquid droplet ranges from 20 mΐ to 70 mΐ for a well with a primary area having 6 mm diameter and a depth of 0.7 mm from the hydrophobic surface. In some cases, the volume of the liquid may vary based on the diameter and the depth of the primary area 112. For example, a well with primary area 112 having an increased diameter and/or an increased depth can accommodate or hold a droplet of a larger volume.

[00107] Figure 5C illustrates that additional liquid is added to liquid droplet 208-1.

[00108] Figure 5D illustrates that additional liquid is added to both liquid droplets 208-

1 and 208-2. For example, primary areas 112 having 6 mm diameter and 0.7 mm depth along with two adjacent satellite areas (e.g., secondary areas) of 1 mm diameter and 0.5 mm depth can hold up to 70 - 90 mΐ per well. In Figure 5D, the surface tension is sufficient to hold the shape of the liquid droplets. However, due to the additional mass of the added liquid, an external force may easily break the shape of the liquid droplets and the liquid within the liquid droplets may spread over the hydrophobic area 110. [00109] Figure 5E illustrates that, after the additional liquid is added, an external force is applied to the array plate 502. For example, the array plate 502 may be gently swirled to facilitate mixing of the liquid within the liquid droplets. In Figure 5E, due to the external force applied to the array plate 502 (and/or the inertia of the liquid droplets 208-1 and 208-2), the shape of the liquid droplets 208-1 and 208-2 is deformed.

[00110] Figure 5F illustrates that, after a large external force is applied, the liquid droplets 208-1 and 208-2 come into contact with each other and merge into a single contiguous volume of liquid.

[00111] Figures 5G-5K illustrate isometric cross-sectional views of an array plate 502 and a lid 504 in accordance with some embodiments. The lid 504 illustrated in Figures 5G-5K facilitates maintaining liquid droplets 208 on the array plate 502 to remain separate from each other.

[00112] In Figure 5G, the lid 504 has two through-holes 506-1 and 506-2 defined therein. In some embodiments, the through-holes are positioned to align with primary areas 208 of the array plate 502 (e.g., a center of a respective through-hole is aligned with a center of a corresponding primary area, a center of the respective through-hole is above a corresponding primary area even if the center of the respective through-hole is not aligned with the center of the corresponding primary area, or at least a portion of the respective through- hole is located directly above at least a portion of the corresponding primary area even if the center of the respective through-hole is not located directly above any portion of the corresponding primary area).

[00113] In some embodiments, the entire lid 504 is made of a hydrophilic material. In some embodiments, at least a bottom surface of the lid 504 is a hydrophilic surface. In some embodiments, at least portions of the bottom surface of the lid 504 adjacent to the through- holes 506 are hydrophilic surfaces. In some embodiments, at least a portion of a side wall of a respective through-hole 506 is a hydrophilic surface. In some embodiments, an entire side wall of the respective through-hole 506 is a hydrophobic surface. In some embodiments, the lid 504 includes one or more hydrophilic coatings on a hydrophobic material.

[00114] In some embodiments, the bottom surface of the lid 504 is a hydrophobic surface and at least a portion of a side wall of the respective through-hole 506 is a hydrophilic surface (or a surface having a hydrophobicity less than a hydrophobicity of the bottom surface of the lid 504). For example, in some cases, the entire lid 504 is made of a hydrophobic material (e.g., polypropylene, polyethylene, cyclic olefin, or polystyrene), and the side wall of the respective through-hole 506 is coated with non-fouling coating that repels proteins and/or cells including but not limited to a surface passivated by albumin of bovine serum albumin (BSA) or fetal bovine serum (FBS), milk, polyethylene glycol, phosphocholine or any other known coating of such functionality. In some embodiments, the entire lid 504 made of a hydrophobic material is coated with the non-fouling coating.

[00115] Figure 5H illustrates that additional liquid is added to the liquid droplet 208-1.

[00116] Figure 51 illustrates that as the volume of the liquid droplet 208-1 continues to increase, the liquid droplet 208-1 comes in contact with the lid 504, in particular an area of the lid 504 adjacent to the through-hole 506-1 defined in the lid 504. Due to the surface tension between the liquid droplet 208-1 and the lid 504, the liquid droplet 208-1 can maintain its shape better even when an external force is applied.

[00117] Figure 5J illustrates that the liquid droplet 208-1 is also in contact with the lid 504, in particular, an area of the lid 504 adjacent to the through-hole 506-2. The lid 504 facilitates the liquid droplets 208-1 and 208-2 maintain their shapes. Thus, even when an external force is applied (e.g., when the array plate 502 is swirled or otherwise agitated), the liquid droplets 208-1 and 208-2 remain separated from each other.

[00118] Figure 5K illustrates that the lid 504 is separated from the array plate 502 while at least one liquid droplet 208 (e.g., liquid droplet 208-1) is in contact with both the array plate 502 and the lid 504. For example, the lid 504 is lifted away from the array plate 502 while the array plate remains stationary, or the array plate 502 is moved away from the lid 504 while the lid 504 remains stationary (e.g., the array plate 502 is lowered). Alternatively, both the lid 504 and the array plate 502 are moved away from each other.

[00119] As shown in Figure 5K, a first portion 208-1 A of liquid droplet 208-1 remains in contact with the lid 504 while a second portion 208-1B of liquid droplet 208-1 remains contact with the array plate 502 while the lid 504 is separated from the array plate 502. Once the lid 504 is separated from the array plate 502 by more than a threshold distance, the first portion 208-1A of the liquid droplet and the second portion 208-1B of the liquid droplet are separated from each other (e.g., the liquid droplet 208-1 is separated into two parts). In some embodiments, a shape of the through-hole 506 defined in the lid 504 and/or an area of a hydrophilic surface adjacent to the through-hole 506 are selected so that only a preselected volume of the liquid droplet remains in contact with the lid 504 when the lid 504 is separated from the array plate 502 (e.g., the lid 504 is configured to remove a preselected volume from the liquid droplet 208). In some cases, the lid 504 is configured to leave less than 500 pl of liquid droplet 208-1, less than 400 mΐ of liquid droplet 208-1, less than 300 mΐ of liquid droplet 208-1, less than 200 mΐ of liquid droplet 208-1, less than 100 mΐ of liquid droplet 208-1, less than 90 mΐ of liquid droplet 208-1, less than 80 mΐ of liquid droplet 208-1, less than 70 mΐ of liquid droplet 208-1, less than 60 mΐ of liquid droplet 208-1, less than 50 mΐ of liquid droplet 208-1, less than 40 mΐ of liquid droplet 208-1, less than 30 mΐ of liquid droplet 208-1, less than 20 mΐ of liquid droplet 208-1, or less than 10 mΐ of liquid droplet 208-1.

[00120] Figure 5L is a cross-sectional view of a combination of a first lid 504 and a second lid 514 in accordance with some embodiments. In some embodiments, the first lid 504 described above with respect to Figures 5G-5K is used in combination with the second lid 514. The second lid 514 is configured to mechanically couple with the first lid 504 (e.g., with a mating mechanism). When the second lid 514 is coupled with the first lid 504, the combination is impermeable (e.g., the through-holes in the first lid 504 are blocked by the second lid 514 so that no liquid can pass through the through-holes in the first lid 504). In some embodiments, the second lid 514 has one or more holes, which are blocked by the first lid 504 when the second lid 514 is coupled with the first lid 504, rendering the combination of the second lid 514 and the first lid 504 impermeable.

[00121] Figures 5M and 5N are cross-sectional views of lids in accordance with some embodiments.

[00122] Figure 5M illustrates a lid 520 that includes one or more legs 522 (or side walls) that extend below the bottom surface of the through-holes. The one or more legs 522 facilitate maintaining a predefined distance between the bottom surface of the through-holes and the hydrophobic area on the array plate. In some embodiments, the one or more legs 522 have a height of at least 1 mm, at least 2 mm, at least 3 mm, at least 4 mm, at least 5 mm, at least 6 mm, at least 7 mm, at least 8 mm, at least 9 mm, at least 10 mm, at least 12 mm, at least 15 mm, at least 20 mm, at least 25 mm, or at least 30 mm. In some embodiments, the one or more legs 522 have a height of at most 2 mm, at most 3 mm, at most 4 mm, at most 5 mm, at most 6 mm, at most 7 mm, at most 8 mm, at most 9 mm, at most 10 mm, at most 12 mm, at most 15 mm, at most 20 mm, at most 25 mm, at most 30 mm, or at most 50 mm.

[00123] Figure 5N illustrates a lid 530 with a bottom surface that includes a non-flat surface 532 (e.g., a curved surface). The shape of the bottom surface of the lid 504 (e.g., a radius of curvature) is selected so that only a preselected volume of the liquid droplet remains in contact with the lid 504 when the lid 504 is separated from the array plate 502 (e.g., the lid 504 is configured to remove a preselected volume from the liquid droplet 208). [00124] Figure 6A illustrates an isometric cross-sectional view of an array plate 602 in accordance with some embodiments. The array plate 602 includes a primary area 112. In Figure 6A, the liquid droplet 208 is located on the primary area 112. A hydrophobic area 110 surrounds the primary area 112.

[00125] A liquid droplet 208 on the array plate 602 has a high air-interfaced-area-to- volume ratio compared to a liquid droplet in a well. Because air is considered to be hydrophobic, in some cases, the increased air-liquid interface causes the adsorption of hydrophobic molecules (e.g., hydrophobic proteins) at the air-liquid interface (e.g., hydrophobic proteins are aggregated around the air-liquid interface instead of spreading throughout the liquid droplet). In some cases, the adsorption of hydrophobic proteins at air- liquid interface leads to a lower concentration of hydrophobic proteins in the liquid droplet different from a true concentration of the hydrophobic proteins within the liquid droplet. In some cases, this adsorption (and resulting physical separation between hydrophobic molecules and hydrophilic molecules) reduces interaction between hydrophobic molecules and hydrophilic molecules, which in some cases interferes with assays based on the interaction between hydrophobic molecules and hydrophilic molecules (e.g., assays indicate lower amounts of hydrophobic molecules and/or hydrophilic molecules than those present in the liquid droplet due to the reduced interaction between the hydrophobic molecules and hydrophilic molecules).

[00126] The air-liquid interface can be reduced significantly by placing a solid surface (e.g., a lid) against the liquid instead of air. Because air is considered to be one of the most hydrophobic state in nature, the replacement of air with a solid surface (typically having less hydrophobicity than the air) is expected to lower the hydrophobicity at the solid-liquid interface. In particular, when a solid surface known to have a lower binding force toward proteins, especially hydrophobic proteins, is exposed to proteins, the adsorption of proteins to the solid surface is reduced significantly. Examples of such solid surface include polypropylene, polystyrene, cyclic olefin, or any combination thereof. Alternatively, a hydrophilic material is coated with a hydrophobic material (e.g., polypropylene, polyethylene, cyclic olefin, or polystyrene). In some embodiments, the lid is made of polypropylene. In some embodiments, the array plate is made of polypropylene.

[00127] Figures 6B and 6C illustrate an array plate 602 and a lid 604 in accordance with some embodiments. [00128] As shown in Figures 6B and 6C, the lid 604 is placed over a hydrophobic area 110 while the liquid droplet 208 is placed on the array plate 602. In some embodiments, the lid 604 is separated from the array plate 602 by a predefine gap. This reduces or prevents wicking (or squeezing) the liquid droplet too far. In some embodiments, a second lid is used in conjunction with the lid 604 (e.g., the second lid is placed over the lid 604 in a manner analogous to the lid 514 described with respect to Figure 5L).

[00129] In some embodiments, the lid 604 is treated to have a non-wetting surface. This reduces the removal of a liquid from the liquid droplet (or clinging of the liquid in the liquid droplet), which, in turn, disruption on cells/beads in the liquid droplet upon the removal of the lid is reduced or eliminated.

[00130] In some embodiments, the entire lid 604 is made of a hydrophobic material. In some embodiments, at least a bottom surface of the lid 604 is a hydrophobic surface. In some embodiments, at least portions of the bottom surface of the lid 604 adjacent to one or more through-holes 606 are hydrophobic surfaces. In some embodiments, at least a portion of a side wall of a respective through-hole 606 is a hydrophobic surface. In some embodiments, an entire side wall of the respective through-hole 606 is a hydrophobic surface. In some embodiments, the lid 604 includes one or more hydrophobic coatings on a hydrophilic material.

[00131] Figures 6D and 6E illustrate an array plate 602 and a lid 614 in accordance with some embodiments. The lid 614 shown in Figures 6D and 6E are similar to the lid 604 shown in Figures 6B and 6C, except that the lid 614 has a through-hole 616, a portion of which has a conical shape. The conical shape reduces the air-liquid interface.

[00132] Figures 7A-7D illustrate a device for facilitating settling of cells (and/or particles) in accordance with some embodiments.

[00133] Figure 7A shows an array plate 702 with an indented primary area. A gasket 704 is located between a hydrophobic grid 706 and the array plate 702. In some embodiments, the gasket 704 is made of hydrophobic material. In some embodiments, the gasket 704 is made of soft, optionally porous, hydrophobic material. The gasket 704 provides water tight sealing between the hydrophobic grid 706 and the array plate 702. In some embodiments, the gasket is soaked with a liquid that is not immiscible with water (e.g., hydrocarbon oil, silicone oil, or perfluorocarbon oil). The combination of the array plate 702, the gasket 704, and the hydrophobic grid 706 is used together as a well. However, in some cases, the hydrophobic grid 706 and the gasket 704 can be separated from the array plate 702, so that the array plate 702 (and the sample thereon) can be used without the high side walls. [00134] In some embodiments, an integrated array plate having the shape of the combination of the array plate 702, the gasket 704, and the hydrophobic grid is used. In some embodiments, the bottom of a well defined in the integrated array plate has a hydrophilic surface and the side wall of the well defined in the integrated array plate has a hydrophobic surface.

[00135] When the liquid 708 is placed in a well having a high aspect ratio (e.g., having an aspect ratio of at least 3 : 1, 4: 1, 5: 1, 6: 1, 7: 1, 8: 1, 9: 1, or 10: 1), it takes longer for cells and/or particles in the liquid 708 to settle to the bottom of the liquid 708. Thus, there is a need for accelerating the settling of the cells and/or particles in the liquid 708.

[00136] Figure 7B shows an absorber 710 coupled with a rod 712. In some embodiments, the absorber 710 is made of a porous material. In some embodiments, a rod 712 itself is an absorber. In some embodiments, the porous material has a pore size less than 5 pm, less than 4 pm, less than 3 pm, less than 2 pm, or less than 1 pm. This reduces or prevents cells or particles having a size greater than the pore size from being trapped in the pores of the porous material.

[00137] Figure 7C shows that the absorber 710 is inserted into the liquid 708 and at least a portion of the liquid 708 is absorbed by the absorber 710.

[00138] Figure 7D shows that the absorber 710 is lowered further, and the cells and/or the particles have moved toward the array plate 702. As shown in Figures 7A-7D, the absorption of the liquid 708 with the absorber 710 has accelerated settlement of the cells and/or the particles.

[00139] Figures 7E and 7F illustrate devices for facilitating settling of cells (and/or particles) in accordance with some embodiments.

[00140] Figure 7E shows that an absorber having a shape of a rod is used (instead of using a combination of an absorber and a separate rod as shown in Figure 7D).

[00141] Figure 7F shows a lid 716 coupled with a plurality of rods 712. Each rod 712 shown in Figure 7F is coupled with a respective absorber 710 . In some embodiments, the absorbers are positioned (and spaced apart) to match the positions of primary areas of an array plate. This allows that the plurality of absorbers 710 is concurrently inserted into a plurality of wells so that particles in respective wells can move rapidly toward the array plate.

[00142] Although various figures herein illustrate array plates with one or two primary areas, array plates with a plurality of primary areas (e.g., the array plate 100 shown in Figure 1 A) may be used in analogous manners. For brevity, such details are not repeated herein. [00143] In light of these principles and examples, we now turn to certain embodiments.

[00144] In accordance with some embodiments, an apparatus (e.g., washer 302 shown in Figure 3A) for washing an array plate includes a plate mount (e.g., plate mount 304) for placing the array plate. The apparatus also includes one or more aspirators (e.g., aspirator 310). A respective aspirator of the one or more aspirators is configured to aspirate a liquid on the array plate. The respective aspirator includes a nozzle, a tip of the nozzle pointed in a non vertical direction (e.g., nozzle 312 in Figure 3 A is pointed in a horizontal direction).

[00145] In some embodiments, the apparatus also includes one or more dispensers (e.g., dispenser 180). A respective dispenser of the one or more dispensers is configured to dispense a wash liquid on the array plate.

[00146] In some embodiments, the respective aspirator includes a needle that includes the nozzle. For example, a nozzle located at the tip of the respective aspirator defines a needle.

[00147] In some embodiments, the needle is a straight needle mounted in the non vertical direction (e.g., needle 316 in Figure 3C).

[00148] In some embodiments, the needle is a curved needle (e.g., needle 314 in Figure 3B) having a first end portion and a second end portion that is opposite to the first end portion. The first end portion is coupled to the rest of the respective aspirator in a direction that is distinct from the non-vertical direction and the second end portion being pointed in the non vertical direction (e.g., needle 314 in Figure 3B is connected to the rest of the aspirator 310 in a vertical direction and the tip of needle 314 is pointed in a horizontal direction).

[00149] In accordance with some embodiments, an apparatus (e.g., washer 402 in Figure 4A) for washing an array plate includes one or more aspirators. A respective aspirator of the one or more aspirators is configured to aspirate a liquid on the array plate. The apparatus includes a plate mount rotatably coupled to a fulcrum, allowing the plate mount to tilt to: a first tilt position at a first time and a second tilt position at a second time that is distinct from the first time (e.g., plate mount 404 in Figure 4A is rotatably coupled to fulcrum 406). The apparatus includes a first set of one or more actuators (e.g., actuator 408) coupled with the plate mount and configured to rotate the plate mount between the first tilt position and the second tilt position.

[00150] In some embodiments, the apparatus also includes one or more dispensers (e.g., dispenser 180). A respective dispenser of the one or more dispensers is configured to dispense a wash liquid on the array plate. [00151] In some embodiments, the apparatus includes one or more processors (e.g., processor 410) configured to: initiate the first set of one or more actuators to rotate the plate mount in the first tilt position to the second tilt position; and initiate, while the array plate is located on the plate mount in the second tilt position, the respective aspirator to aspirate a liquid from the array plate.

[00152] In some embodiments, the apparatus includes a second set of one or more actuators (e.g., actuator 192) configured to position the respective aspirator. The array plate includes a plurality of hydrophilic regions surrounded by one or more hydrophobic regions. A respective hydrophilic region of the plurality of hydrophilic regions includes a primary area having one or more indentations and one or more secondary areas, adjacent to the primary area (e.g., Figure 2H). The respective aspirator is configured to aspirate a liquid from at least one secondary area of the one or more secondary areas for the respective hydrophilic region.

[00153] In accordance with some embodiments, a method for removing a liquid on an array plate includes obtaining an array plate with a liquid droplet thereon; placing at least a tip of a curved needle of an aspirator in the liquid droplet; and while at least the tip of the curved needle remains in the liquid droplet, aspirating at least a portion of the liquid droplet with the aspirator (e.g., Figure 3B).

[00154] In some embodiments, the array plate includes a plurality of hydrophilic regions surrounded by one or more hydrophobic regions, a respective hydrophilic region of the plurality of hydrophilic regions including one or more indentations.

[00155] In some embodiments, the respective hydrophilic region includes a primary area that corresponds to at least a portion of the one or more indentations and one or more secondary areas adjacent to the primary area. The method includes aspirating at least the portion of the liquid droplet with the aspirator while at least the tip of the curved needle is placed adjacent to one of the one or more secondary areas (e.g., Figure 3B).

[00156] In accordance with some embodiments, a method for removing a liquid on an array plate includes obtaining an array plate with a liquid droplet thereon (e.g., Figure 4A); tilting the array plate so that the array plate is in a non-horizontal position (e.g., Figure 4C); and while the array plate is in the non-horizontal position, aspirating at least a portion of the liquid droplet with an aspirator (e.g., Figure 4D).

[00157] In some embodiments, the residual liquid after aspiration is further drained by tilting a plate. Upon removal of the liquid by aspirator, a plate is left with residual volume, for example 20 - 25 pl for primary areas 112 each having 6 mm diameter and 0.7 mm depth along with two satellite wells (e.g., secondary areas) having 1 mm diameter and 0.5 mm depth. The residual liquid of 20 - 25 mΐ can be further removed by placing an absorbent material at a satellite well (e.g., a secondary area) used for dispensing a washing fluid preferably with tilting of a plate where a dispensing satellite well is at a lower position than primary areas (e.g., wicking the residual liquid with the absorbent material). In some embodiments, tilting the plate between 5 degrees and 85 degrees allows most of residual liquid collects at a dispensing satellite well while cells (or particles) remain in primary areas or aspiration satellite well so that the residual liquid can be removed from the dispensing satellite well. In some embodiments, the plate is tilted between 25 degrees and 65 degrees for removing the residual liquid from the dispensing satellite well.

[00158] In some embodiments, the array plate includes a plurality of hydrophilic regions surrounded by one or more hydrophobic regions, a respective hydrophilic region of the plurality of hydrophilic regions including one or more indentations.

[00159] In some embodiments, the respective hydrophilic region includes a primary area that corresponds to at least a portion of the one or more indentations and one or more secondary areas adjacent to the primary area. The method includes: tilting the array plate so that at least one secondary area of the one or more secondary areas is located lower than the primary area (e.g., Figure 4C); and aspirating at least the portion of the liquid droplet with the aspirator while a nozzle of the aspirator is located adjacent to at least the one secondary area located lower than the primary area (e.g., Figure 4D).

[00160] In accordance with some embodiments, a first lid (e.g., lid 504 in Figure 5G) for use in washing of a sample on an array plate includes a cover plate having a first surface and a second surface that is opposite to the first surface. A plurality of distinct and separate indentations (e.g., through-hole features or dimples) is defined on the second surface.

[00161] In some embodiments, the plurality of distinct and separate indentations is arranged to correspond to a plurality of hydrophilic regions of the array plate surrounded by one or more hydrophobic regions of the array plate.

[00162] In some embodiments, a respective indentation of the plurality of distinct and separate indentations includes a hydrophilic surface.

[00163] In some embodiments, the cover plate defines a respective through-hole, extending from the first surface to the second surface, for a respective indentation of the plurality of distinct and separate indentations. [00164] In some embodiments, a respective indentation of the plurality of distinct and separate indentations has a curved surface (e.g., a dome-shaped surface, such as a hemispherical surface as shown in Figure 5N)

[00165] In accordance with some embodiments, a combination of any first lid described herein (e.g., lid 504) and a second lid (e.g., lid 514 in Figure 5L) that is distinct and separate from the first lid. The first lid and the second lid are configured to removably couple with each other. The second lid, at least when coupled with the first lid, is impermeable.

[00166] In accordance with some embodiments, a method includes obtaining an array plate; and placing any first lid described herein on the array plate.

[00167] In some embodiments, the method also includes placing a droplet on the array plate (e.g., prior to placing the first lid on the array plate or after the first lid is placed on the array plate, through a through-hole in the first lid).

[00168] In some embodiments, the droplet is placed on the array plate prior to placing the first lid on the array plate.

[00169] In some embodiments, the method includes, subsequent to placing the first lid on the array plate, placing the droplet on the array plate through a through-hole defined in the first lid.

[00170] In some embodiments, the method includes moving the first lid away from the array plate while maintaining a first portion of a droplet so that the first portion of the droplet is separated from a second portion of the droplet remaining on the array plate (e.g., Figure 5K).

[00171] In accordance with some embodiments, a lid (e.g., the lid 604 in Figure 6B) for use on an array plate includes a cover plate having a first surface and a second surface that is opposite to the first surface. The second surface is configured to be placed toward the array plate and the second surface is flat.

[00172] In some embodiments, the second surface includes a hydrophobic surface.

[00173] In some embodiments, the second surface includes a non-wetting surface.

[00174] In some embodiments, the lid includes one or more protrusions to provide a gap between the second surface of the lid and the array plate when the lid is placed on the array plate. For example, the lid 604 in Figure 6B may have one or more legs analogous to the one or more legs 522 described with respect to Figure 5M.

[00175] In accordance with some embodiments, a combination of any lid described herein and an array plate that is distinct and separate from the lid. [00176] In some embodiments, one or more of the lid and the array plate include one or more protrusions to provide a gap between the second surface of the lid and the array plate when the lid is placed on the array plate (e.g., the lid, the array plate, or both have one or more legs to maintain a distance between the lid and the array plate when the lid is placed on the array plate).

[00177] In some embodiments, the array plate includes a particular material, and at least the second surface of the cover plate includes the particular material. For example, both the array plate and the lid are made of a same material (e.g., polypropylene).

[00178] In accordance with some embodiments, a method includes obtaining an array plate; and, while a liquid droplet remains on the array plate, placing on the array plate a lid that includes a cover plate having a first surface and a second surface that is opposite to the first surface so that the second surface of the lid is placed toward the array plate (e.g., Figure 6C). The second surface is flat.

[00179] In some embodiments, the method includes, after placing the lid on the array plate, moving the lid away from the array plate so that the lid is separated from the liquid droplet and the liquid droplet remains on the array plate (e.g., the lid is made of a non-wetting material or includes a non-wetting coating).

[00180] In accordance with some embodiments, a device for at least partial insertion into a well includes a rod (e.g., rod 712 in Figure 7B) having a first end and a second end that is opposite to the first end; and one or more absorbers (e.g., absorber 710) located adjacent to the first end of the rod, wherein the one or more absorbers include a porous material.

[00181] In some embodiments, wherein the porous material has a pore size of 5 pm or less. The device of claim 35, wherein the porous material has a pore size of 3 pm or less. The device of claim 36, wherein the porous material has a pore size of 1 pm or less.

[00182] In some embodiments, the porous material extends from the first end to the second end (e.g., the porous material envelops the rod as shown in Figure 7E). In some embodiments, the porous material extends from the first end but does not extend to the second end (e.g., Figure 7D). In some embodiments, the one or more absorbers include a first absorber including a first porous material and a second absorber that is distinct and separate from the first absorber including a second porous material that is distinct from the first porous material. For example, the porosity or other characteristics of a particular porous material is selected depending on the location of the particular porous material within a rod. For example, a rod may include a filter membrane at the bottom filled with another porous material contained within a housing with opening(s) at the bottom and/or side (e.g., a first porous material is partially embedded in a second porous material and partially exposed from the second porous material from a bottom and/or one or more sides of the second porous material).

[00183] In some embodiments, the one or more absorbers collectively constitute the rod. For example, in some cases, the rod is made entirely of a porous material.

[00184] In some embodiments, the device (e.g., the device shown in Figure 7F) includes a plate (e.g., lid 716), a plurality of rods (e.g., rods 712), and multiple groups of one or more absorbers (e.g., absorbers 710). A respective group of one or more absorbers of the multiple groups of one or more absorbers is distinct and separate from any other group of one or more absorbers of the multiple groups of one or more absorbers (e.g., each group of one or more absorbers is coupled to a respective rod). The respective group of one or more absorbers is located adjacent to an end of a respective rod of the plurality of rods (e.g., each group of one or more absorbers is coupled to a tip of a respective rod).

[00185] In accordance with some embodiments, a method includes obtaining a well containing a solution; inserting one or more absorbers at least partially into the well so that at least a portion of the solution is absorbed by the one or more absorbers (e.g., Figures 7B-7D); and, subsequent to inserting the one or more absorbers at least partially into the well, separating the one or more absorbers and the well so that the one or more absorbers cease to be placed at least partially in the well (e.g., the one or more absorbers are taken out of the well).

[00186] In accordance with some embodiments, a method includes obtaining an array plate defining a plurality of wells; concurrently inserting respective groups of one or more absorbers at least partially into respective wells of the plurality of wells so that at least a portion of a solution in a respective well is absorbed by a respective group of one or more absorbers (e.g., absorbers 710 shown in Figure 7F are concurrently inserted into corresponding wells); and, subsequent to concurrently inserting the respective groups of one or more absorbers at least partially into the respective wells, separating the plate and the array plate (e.g., after the liquid in wells are absorbed, the absorbers 710 are removed from the wells).

[00187] Figures 8A-8C illustrate perspective views of array plates in accordance with some embodiments.

[00188] Figure 8 A illustrates array plate 102, which is similar to array plate 102 shown in Figure 1B except that hydrophilic regions 812 (e.g., hydrophilic regions 812-1 through 812- 8) have a substantially rectangular shape (e.g., a rectangular shape, or a rectangular shape with corner rounding or chamfers). Hydrophilic regions 812 with a substantially rectangular shape facilitate laminar flow of liquid during dispensing or aspiration, which improves retention of cells (or particles) on hydrophilic regions 812.

[00189] Figure 8B illustrates array plate 102, which is similar to array plate 102 shown in Figure 8A except that a hydrophilic region has primary region 812 and one or more secondary regions 814 and 816. As shown in Figure 8B, in some embodiments, one or more secondary regions 814 and 816 are indented from (e.g., positioned lower than) hydrophobic region 110 and primary region 812 is indented from (e.g., positioned lower than) secondary regions 814 and 816.

[00190] Figure 8C illustrates that a dispenser with dispenser 880 with a rectangular tip (or nozzle) is used for dispensing liquid to array plate 102 shown in Figure 8B and/or aspirator 890 with a rectangular tip (or nozzle) is used for aspirating liquid from array plate 102 shown in Figure 8B. Dispenser 880 with a rectangular tip (or nozzle) and aspirator 890 with a rectangular tip (or nozzle) facilitate providing a laminar flow on a respective hydrophilic region, which improves retention of cells (or particles) on the respective hydrophilic region.

[00191] Figure 8D illustrates an example array plate in accordance with some embodiments.

[00192] Section (A) of Figure 8D illustrates an array plate in which the primary area 812 extending between the secondary areas 814 and 816 is a rectangular area. In some embodiments, each of the secondary areas 814 and 816 is also a rectangular area.

[00193] Section (A) of Figure 8D also illustrates that the primary area 812 has a particular width 818 adjacent to one of the two secondary areas (e.g., the secondary area 814), the primary area 812 has a width 822 (which is equal to the width 818) adjacent to the other of the two secondary areas (e.g., he secondary area 816); and the primary area 812 has a width 820 which is equal to the width 818) between the two secondary areas 814 and 816.

[00194] The primary area 812 shown in Section (A) of Figure 8D has a uniform width between the two secondary areas 814 and 816. In some embodiments, the primary area 812 has a particular width 818 at a first location along an axis extending between the two secondary areas (e.g., line AA’), the first location having a first distance from a particular secondary area of the two secondary areas, the same width 820 at a second location along the axis extending between the two secondary areas, the second location having a second distance from the particular secondary area that is distinct from the first distance, the same width 822 at a third location along the axis extending between the two secondary areas, the third location having a third distance from the particular secondary area that is distinct from the first distance and the second distance.

[00195] In some embodiments, the two secondary areas 814 and 816 have the same width as the primary area 812.

[00196] Line AA’ in Section (A) of Figure 8D indicates a view from which cross-section shown in Section (C) or (D) of Figure 8D is taken.

[00197] Section (B) of Figure 8D illustrates an array plate, which is similar to the array plate shown in Section (A) of Figure 8D, except that the secondary areas 814 and 816 are substantially rectangular (but not perfectly rectangular). For example, the secondary areas 814 and 816 shown in Section (B) of Figure 8D have rounded comers.

[00198] Section (C) of Figure 8C illustrates that the primary area 812 and the secondary areas 814 and 816 are offset from the surrounding hydrophobic area by a same distance.

[00199] Section (D) of Figure 8C illustrates that the primary area 812 is offset from the surrounding hydrophobic area by a first distance 830 and the secondary areas 814 and 816 are offset from the surrounding hydrophobic area by a second distance 832 that is distinct from the first distance 830.

[00200] In some embodiments, the primary area 812 is offset from the surrounding hydrophobic area by at least 1.7 mm. In some embodiments, the primary area is offset from the surrounding hydrophobic area by at least 2 mm. In some embodiments, the primary area is offset from the surrounding hydrophobic area by at least 4 mm.

[00201] Figure 8E illustrates numerical analysis results of flow over a rectangular hydrophobic area having respective depths in accordance with some embodiments. The cell loss in array plates with the rectangular hydrophilic areas is significantly lower than the cell loss in the array plates with round hydrophilic areas (as shown in Figures 6G and 6H). For example, the streamlines shown in chart (A) of Figure 8E shows that liquid propagates from the left side (where the liquid is dispensed) toward the right side (where the liquid is aspirated) without forming a vortex over a hydrophilic area that is indented by 1 mm. The pressure profile illustrated in chart (B) of Figure 8E shows that there is negligible pressure gradient within the liquid located on the hydrophilic area that is indented by 1 mm. Furthermore, the streamlines shown in chart (C) of Figure 8E shows that liquid propagates from the left side toward the right side without forming a vortex over a hydrophilic area even when the hydrophilic area is indented by as much as 4 mm. The pressure profile illustrated in chart (D) of Figure 8E shows that there is negligible pressure gradient within the liquid located on the hydrophilic area that is indented by 4 mm. Thus, utilizing a rectangular hydrophilic area (or a hydrophilic area with a uniform width) can reduce the cell loss.

[00202] Although the numerical analysis shown in Figure 8E was performed a hydrophilic area having a length of 6 mm, a person having ordinary skill in the art would understand that the reduced cell loss can be observed with a hydrophilic area with different lengths.

[00203] Various aspects and characteristics of the methods of using the array plates described above are applicable to array slides (e.g., adding one or more solutions to one or more liquid droplets of the respective liquid droplets, performing an immunoassay, and washing a respective liquid droplets), and vice versa. Because these aspects and characteristics are described above, they are not repeated herein for brevity.

[00204] It is well known to a person having ordinary skill in the art that array slides and plates can be used in many other biological and chemical reactions. Therefore, such details and specific examples are omitted for brevity.

[00205] The foregoing description, for purpose of explanation, has been described with reference to specific embodiments. However, the illustrative discussions above are not intended to be exhaustive or to limit the embodiments to the precise forms disclosed. Many modifications and variations are possible in view of the above teachings. The embodiments were chosen and described in order to best explain the principles of the invention and its practical applications, to thereby enable others skilled in the art to best utilize the invention and various embodiments with various modifications as are suited to the particular use contemplated.

Claims

What is claimed is:

1. An apparatus for washing an array plate, the apparatus comprising:

a plate mount for placing the array plate; and

one or more aspirators, a respective aspirator of the one or more aspirators configured to aspirate a liquid on the array plate,

wherein the respective aspirator includes a nozzle, a tip of the nozzle pointed in a non vertical direction.

2. The apparatus of claim 1, wherein:

the respective aspirator includes a needle that includes the nozzle.

3. The apparatus of claim 2, wherein:

the needle is a straight needle mounted in the non-vertical direction.

4. The apparatus of claim 2, wherein:

the needle is a curved needle having a first end portion and a second end portion that is opposite to the first end portion, the first end portion being coupled to the rest of the respective aspirator in a direction that is distinct from the non-vertical direction and the second end portion being pointed in the non-vertical direction.

5. An apparatus for washing an array plate, the apparatus comprising:

one or more aspirators, a respective aspirator of the one or more aspirators configured to aspirate a liquid on the array plate;

a plate mount rotatably coupled to a fulcrum, allowing the plate mount to tilt to: a first tilt position at a first time and a second tilt position at a second time that is distinct from the first time; and

a first set of one or more actuators coupled with the plate mount and configured to rotate the plate mount between the first tilt position and the second tilt position.

6. The apparatus of claim 5, including:

one or more processors configured to:

initiate the first set of one or more actuators to rotate the plate mount in the first tilt position to the second tilt position; and initiate, while the array plate is located on the plate mount in the second tilt position, the respective aspirator to aspirate a liquid from the array plate.

7. The apparatus of any of claims 1-6, further comprising:

a second set of one or more actuators configured to position the respective aspirator, wherein:

the array plate includes a plurality of hydrophilic regions surrounded by one or more hydrophobic regions, a respective hydrophilic region of the plurality of hydrophilic regions including a primary area having one or more indentations and one or more secondary areas, adjacent to the primary area; and

the respective aspirator is configured to aspirate a liquid from at least one secondary area of the one or more secondary areas for the respective hydrophilic region.

8. A method for removing a liquid on an array plate, the method comprising:

obtaining an array plate with a liquid droplet thereon;

placing at least a tip of a curved needle of an aspirator in the liquid droplet; and while at least the tip of the curved needle remains in the liquid droplet, aspirating at least a portion of the liquid droplet with the aspirator.

9. The method of claim 8, wherein:

the array plate includes a plurality of hydrophilic regions surrounded by one or more hydrophobic regions, a respective hydrophilic region of the plurality of hydrophilic regions including one or more indentations.

10. The method of claim 9, wherein:

the respective hydrophilic region includes a primary area that corresponds to at least a portion of the one or more indentations and one or more secondary areas adjacent to the primary area; and

the method includes aspirating at least the portion of the liquid droplet with the aspirator while at least the tip of the curved needle is placed adjacent to one of the one or more secondary areas.

11. A method for removing a liquid on an array plate, the method comprising:

obtaining an array plate with a liquid droplet thereon;

tilting the array plate so that the array plate is in a non-horizontal position; and while the array plate is in the non-horizontal position, aspirating at least a portion of the liquid droplet with an aspirator.

12. The method of claim 11, wherein:

13. The method of claim 12, wherein:

the method includes:

tilting the array plate so that at least one secondary area of the one or more secondary areas is located lower than the primary area; and

aspirating at least the portion of the liquid droplet with the aspirator while a nozzle of the aspirator is located adjacent to at least the one secondary area located lower than the primary area.

14. A first lid for use in washing of a sample on an array plate, the first lid comprising: a cover plate having a first surface and a second surface that is opposite to the first surface, a plurality of distinct and separate indentations defined on the second surface.

15. The first lid of claim 14, wherein:

the plurality of distinct and separate indentations is arranged to correspond to a plurality of hydrophilic regions of the array plate surrounded by one or more hydrophobic regions of the array plate.

16. The first lid of claim 14 or 15, wherein:

a respective indentation of the plurality of distinct and separate indentations includes a hydrophilic surface.

17. The first lid of any of claims 14-16, wherein:

the cover plate defines a respective through-hole, extending from the first surface to the second surface, for a respective indentation of the plurality of distinct and separate indentations.

18. The first lid of any of claims 14-17, wherein:

a respective indentation of the plurality of distinct and separate indentations has a curved surface.

19. A combination of the first lid of any of claims 14-18 and a second lid that is distinct and separate from the first lid, wherein:

the first lid and the second lid are configured to removably couple with each other; and

the second lid, at least when coupled with the first lid, is impermeable.

20. A method, comprising:

obtaining an array plate; and

placing the first lid of any of claims 14-19 on the array plate.

21. The method of claim 20, further comprising:

placing a droplet on the array plate.

22. The method of claim 21, wherein the droplet is placed on the array plate prior to placing the first lid on the array plate.

23. The method of claim 21, including:

subsequent to placing the first lid on the array plate, placing the droplet on the array plate through a through-hole defined in the first lid.

24. The method of any of claims 20-23, further comprising:

moving the first lid away from the array plate while maintaining a first portion of a droplet in contact with the first lid so that the first portion of the droplet is separated from a second portion of the droplet remaining on the array plate.

25. A lid for use on an array plate, the lid comprising:

a cover plate having a first surface and a second surface that is opposite to the first surface, wherein the second surface is configured to be placed toward the array plate and the second surface is flat.

26. The lid of claim 25, wherein:

the second surface includes a hydrophobic surface.

27. The lid of claim 25 or 26, wherein:

the second surface includes a non-wetting surface.

28. The lid of any of claims 25-27, including:

one or more protrusions to provide a gap between the second surface of the lid and the array plate when the lid is placed on the array plate.

29. A combination of the lid of any of claims 25-28 and an array plate that is distinct and separate from the lid.

30. The combination of claim 29, wherein:

one or more of the lid and the array plate include one or more protrusions to provide a gap between the second surface of the lid and the array plate when the lid is placed on the array plate.

31. The combination of claim 29 or 30, wherein:

the array plate includes a particular material; and

at least the second surface of the cover plate includes the particular material.

32. A method, comprising:

obtaining an array plate; and

while a liquid droplet remains on the array plate, placing on the array plate a lid that includes a cover plate having a first surface and a second surface that is opposite to the first surface so that the second surface of the lid is placed toward the array plate, wherein the second surface is flat.

33. The method of claim 32, including:

after placing the lid on the array plate, moving the lid away from the array plate so that the lid is separated from the liquid droplet and the liquid droplet remains on the array plate.

34. A device for at least partial insertion into a well, the device comprising:

a rod having a first end and a second end that is opposite to the first end; and one or more absorbers located adjacent to the first end of the rod, wherein the one or more absorbers include a porous material.

35. The device of claim 34, wherein the porous material has a pore size of 5 pm or less.

36. The device of claim 35, wherein the porous material has a pore size of 3 pm or less.

37. The device of claim 36, wherein the porous material has a pore size of 1 pm or less.

38. The device of any of claims 34-37, wherein the porous material extends from the first end to the second end.

39. The device of any of claims 34-38, wherein the one or more absorbers collectively constitute the rod.

40. The device of any of claims 34-39, wherein:

the device includes a plate, a plurality of rods, and multiple groups of one or more absorbers;

a respective group of one or more absorbers of the multiple groups of one or more absorbers is distinct and separate from any other group of one or more absorbers of the multiple groups of one or more absorbers; and

the respective group of one or more absorbers is located adjacent to an end of a respective rod of the plurality of rods.

41. A method, comprising:

obtaining a well containing a solution;

inserting the one or more absorbers of the device of any of claims 34-40 at least partially into the well so that at least a portion of the solution is absorbed by the one or more absorbers; and

subsequent to inserting the one or more absorbers at least partially into the well, separating the one or more absorbers and the well so that the one or more absorbers cease to be placed at least partially in the well.

42. A method comprising:

obtaining an array plate defining a plurality of wells;

concurrently inserting respective groups of one or more absorbers of the device of claim 40 at least partially into respective wells of the plurality of wells so that at least a portion of a solution in a respective well is absorbed by a respective group of one or more absorbers; and sub sequent to concurrently inserting the respective groups of one or more absorbers at least partially into the respective wells, separating the plate and the array plate.

43. A device, comprising:

a plate having:

an array of hydrophilic areas; and

one or more hydrophobic areas surrounding the array of hydrophilic, wherein: a respective hydrophilic area of the array of hydrophilic areas is indented from a surrounding hydrophobic area of the one or more hydrophobic areas.

44. The device of claim 43, wherein:

the respective hydrophilic area includes at least two secondary areas and a primary area located between the two secondary areas.

45. The device of claim 44, wherein:

the primary area is offset from the surrounding hydrophobic area by a first distance; and

the two secondary areas are offset from the surrounding hydrophobic area by a second distance that is distinct from the first distance.

46. The device of claim 44 or 45, wherein:

the primary area has a rectangular area extending between the two secondary areas.

47. The device of any of claims 44-46, wherein:

the primary area has a particular width adjacent to one of the two secondary areas; the primary area has the particular width adjacent to the other of the two secondary areas; and

the primary area has the particular width between the two secondary areas.

48. The device of any of claims 44-46, wherein:

the primary area has a particular width at a first location along an axis extending between the two secondary areas, the first location having a first distance from a particular secondary area of the two secondary areas;

the primary area has the particular width at a second location along the axis extending between the two secondary areas, the second location having a second distance from the particular secondary area that is distinct from the first distance; and the primary area has the particular width at a third location along the axis extending between the two secondary areas, the third location having a third distance from the particular secondary area that is distinct from the first distance and the second distance.

49. The device of any of claims 44-48, wherein the primary area has a uniform width between the two secondary areas.

50. The device of any of claims 44-49, wherein the two secondary areas have the same width as the primary area.

51. The device of any of claims 44-50, wherein the primary area is offset from the surrounding hydrophobic area by at least 1.7 mm.

52. The device of claim 51, wherein the primary area is offset from the surrounding hydrophobic area by at least 2 mm.

53. The device of claim 52, wherein the primary area is offset from the surrounding hydrophobic area by at least 4 mm.

54. A method, comprising:

obtaining the device of any of claims 43-53, wherein a plurality of cells is located on the respective hydrophilic area; and

washing the plurality of cells by concurrently dispensing liquid adjacent to a first end of the respective hydrophilic area and aspirating liquid adjacent to a second end, opposite to the first end, of the respective hydrophilic area.