Patent Grant
10792661
The disclosed embodiments relate generally to array plates and slides, and methods for making and using the same. More particularly, the disclosed embodiments relate to array plates and slides for biological and/or chemical reactions, and methods for making and using the same.
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.
Polytetrafluoroethylene (PTFE) matrix-coated slides have been used for holding larger volumes of droplets on a microscope slide surface. The 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.
The PTFE matrix-coated slides are typically made by depositing a mixture of resin and PTFE powder on glass slides. The resin in the PTFE matrix holds the PTFE powder together and also onto the glass slides.
However, the PTFE matrix has a lower hydrophobicity than pure PTFE, because the resin in the PTFE matrix has a lower hydrophobicity than the pure PTFE. When the PTFE matrix-coated slides are used in biological/chemical processing, the PTFE matrix is easily contaminated by biological and/or chemical materials used in the biological/chemical processing. For example, proteins in biological samples may attach to the PTFE matrix during biological assays. This leads to contamination of samples and inaccurate assay results.
Accordingly, there is need for plates and slides with hydrophobic surfaces with higher hydrophobicity. Such plates and slides may replace the PTFE matrix-coated slides in performing biological and/or chemical reactions. Such plates and slides reduce or eliminate adsorption of biological and/or chemical materials onto hydrophobic surfaces, thereby reducing contamination of samples and improving accuracy in assays.
A number of embodiments that overcome the limitations and disadvantages of existing array plates and slides are presented in more detail below. These embodiments provide array plates and slides for biological and/or chemical reactions and methods for making and using the same.
As described in more detail below, some embodiments involve a method for manufacturing an array plate. The method includes providing a first structure, the first structure including a sheet layer with a plurality of discrete through holes. The method includes pressing the first structure against a first surface of a mold, providing a heated plastic material into the mold, and cooling the plastic material to form a second structure so that the first structure and the second structure are coupled. The second structure includes a base layer and one or more vertical structures along a periphery of the base layer, adjacent a first surface of the base layer. At least a portion of a first surface of the sheet layer of the first structure is exposed from the second structure, and a second surface of the sheet layer, opposite to the first surface of the sheet layer, is embedded in the base layer of the second structure adjacent the first surface of the base layer.
In accordance with some embodiments, an apparatus includes an array plate manufactured by the aforementioned method.
In accordance with some embodiments, an apparatus includes a first structure, the first structure including a sheet layer with a plurality of discrete through holes. The apparatus includes a second structure coupled to the first structure, the second structure including a base layer and one or more vertical structures along a periphery of the base layer, adjacent a first surface of the base layer. At least a portion of a first surface of the sheet layer of the first structure is exposed from the second structure, and a second surface of the sheet layer, opposite to the first surface of the sheet layer, is embedded in the base layer of the second structure adjacent the first surface of the base layer.
In accordance with some embodiments, a method includes providing an apparatus of the aforementioned apparatuses, the apparatus defining a reservoir. The method includes storing a liquid medium in the reservoir of the apparatus so that the first surface of the sheet layer is covered by the liquid medium, and dispensing respective liquid droplets on respective locations on the base layer. The respective locations correspond to locations of the plurality of discrete through holes defined in the sheet layer, and the respective liquid droplets are immiscible with the liquid medium. In some embodiments, the method includes adding one or more solutions to one or more liquid droplets of the respective liquid droplets. In some embodiments, the method includes performing an immunoassay by: immobilizing one of one or more antibodies and one or more antigens in one or more respective liquid droplets to the base layer; adding one or more solutions to the one or more respective liquid droplets of the respective liquid droplets, at least one of the one or more solutions including the other of the one or more antibodies and the one or more antigens; and detecting a binding of the at least one antigen with at least one antibody in the one or more respective liquid droplets. In some embodiments, the method includes washing the respective liquid droplets on the apparatus by: removing a portion of the liquid medium; adding a wash buffer to the reservoir; shaking the apparatus so that the wash buffer and the respective liquid droplets are mixed; draining at least a portion of the wash buffer from the reservoir; and providing a liquid medium in the reservoir of the apparatus so that the first surface of the sheet layer is covered by the liquid medium.
Some embodiments involve a method for manufacturing an array slide. The method includes providing a first structure in a mold. The first structure includes a sheet layer with a plurality of discrete through-holes. The method also includes providing a heated plastic material into the mold and cooling the plastic material to form a second structure so that the first structure and the second structure are coupled. At least a portion of a first surface of the sheet layer of the first structure is exposed from the second structure, and a second surface of the sheet layer, opposite to the first surface of the sheet layer, is embedded in the second structure.
Some embodiments involve an array slide manufactured by the aforementioned method.
In accordance with some embodiments, an array slide includes a first structure including a sheet layer with a plurality of discrete through-holes; and a second structure coupled to the first structure. At least a portion of a first surface of the sheet layer of the first structure is exposed from the second structure. A top portion of the sheet layer, including the exposed portion of the first surface of the sheet layer, includes at least 95% of fluorocarbon by weight. A second surface of the sheet layer, opposite to the first surface of the sheet layer, is embedded in the second structure.
In accordance with some embodiments, a device includes a first structure with a sheet layer with a plurality of discrete through-holes and a second structure coupled to the first structure. At least a portion of a first surface of the sheet layer of the first structure is exposed from the second structure. A top portion of the sheet layer, including the exposed portion of the first surface of the sheet layer, includes fluorocarbon. The second structure includes a material of a higher surface tension than the top of the sheet layer. A second surface of the sheet layer, opposite to the first surface of the sheet layer, is embedded in the second structure. The second structure extends at least partially into the plurality of discrete through-holes of the first structure.
In accordance with some embodiments, a method includes providing a first structure in a mold, the first structure including a sheet layer with a plurality of discrete through-holes and providing a heated plastic material into the mold. The method also includes cooling the plastic material to form a second structure so that the first structure and the second structure are coupled. At least a portion of a first surface of the sheet layer of the first structure is exposed from the second structure. A top portion of the sheet layer, including the exposed portion of the first surface of the sheet layer, includes fluorocarbon. The second structure includes a material of a higher surface tension than the top of the sheet layer. A second surface of the sheet layer, opposite to the first surface of the sheet layer, is embedded in the second structure. The second structure extends at least partially into the plurality of discrete through-holes of the first structure.
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.
Like reference numerals refer to corresponding parts throughout the drawings.
Array plates and slides and methods for making and using the array plates and slides 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.
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.
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 surface could be termed a second surface, and, similarly, a second surface could be termed a first surface, without departing from the scope of the embodiments. The first surface and the second surface are both surfaces, but they are not the same surface.
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.
The exemplary array plate 110 includes at least a combination of a first structure (e.g., a plate) and a second structure (e.g., a frame). The details of the first structure and the second structure are described with respect to
A plurality of discrete through holes 206 are defined in the sheet layer of the first structure 202. The plurality of discrete through holes 206 are formed by punching holes through the sheet layer of the first structure 202 (which typically includes a polymer). Typically, the plurality of discrete through holes have substantially the same diameter (e.g., with less than 50, 30, 20, 10, or 5% variation among the holes). In some embodiments, a respective through hole has a 1 mm-5 mm diameter, or 2 mm-3 mm diameter. In some embodiments, the discrete through holes are arranged in a predefined pattern. For example, when 96 discrete through holes are defined in the sheet layer of the first structure 202, the 96 discrete through holes are arranged in an 8×12 array. In some embodiments, the discrete through holes have a predefined spacing.
In some embodiments, the sheet layer of the first structure 202 includes at least 50% of fluorocarbon by weight. Alternatively, the sheet layer of the first structure 202 may include at least 60, 70, 80, 90, 95, or 99% of fluorocarbon by weight. In some embodiments, the sheet layer of the first structure 202 includes at least 90% of polytetrafluoroethylene by weight. Alternatively, the sheet layer of the first structure 202 may include at least 50, 60, 70, 80, 95, or 99% of polytetrafluoroethylene by weight.
In some embodiments, a first surface (e.g., a surface facing away from the second structure 204) of the first structure 202 is roughened to increase the hydrophobicity and/or oleophobicity.
In some embodiments, at least the first surface of the first structure 202 is coated with a material of at least 50% of fluorocarbon by weight. The thickness of the coated material may be as thin as 1 nm, 2 nm, 5 nm, or 10 nm.
The second structure 204 includes a base layer 208 and one or more vertical structures 212 along, or adjacent to, a periphery of the base layer 208, adjacent a first surface of the base layer 208 (e.g., a top surface of the base layer 208 facing the first structure 202 as illustrated in
In some embodiments, the base layer 208 of the second structure 204 includes a plurality of structures 210 that correspond to the plurality of discrete through holes in the first structure 202. In some embodiments, the second structure 204 is configured to mate with the first structure 202.
In some embodiments, the one or more vertical structures 212 include a plurality of pins 214. In some embodiments, the plurality of pins 214 vertically protrudes from the rest of the one or more vertical structures (e.g., a tip of a pin 214 is located further away from the rest of the one or more vertical structures). In some embodiments, the pins 214 provide additional stiffness for the one or more vertical structures 212. In some embodiments, the pins 214 also provide additional stiffness for the one or more side walls formed over the one or more vertical structures 212 so that the one or more side walls may maintain a flat top surface. In some embodiments, the pins 214 are used to remove an array plate from a mold, the process of which is described below with respect to
The second structure 204 typically includes a plastic material. In some embodiments, the plastic material includes polycarbonates. In some embodiments, the plastic material includes cyclic olefin polymer or copolymer.
In some embodiments, the plastic material of the second structure 204 is optically transparent. This allows the second structure 204 to be optically imaged from a bottom surface side of the base layer 208 facing away from the first structure 202. In order to obtain high quality images, it is important to keep the first structure and the second structure.
In some embodiments, the combination 220 of the first structure 202 and the second structure 204 is made by forming the second structure 204 through a molding process while the first structure is placed in a mold. The details of the molding process are described with respect to
As shown in
In some embodiments, the first structure 202 and the second structure 204 have a surface tension difference of more than 10 dynes/cm. In some embodiments, the second structure 204 is more hydrophilic than the first structure 202, and the first structure 202 is more hydrophobic than the second structure 204.
In some embodiments, a plurality of pins 242 coupled with the second mold component 240 are spring loaded so that the plurality of pins 242 are configured to apply force on the first structure 202 toward the first mold component 230 when the first mold component 230 and the second mold component 240 are assembled together.
In some embodiments, the bottom surface of the first structure 202 (e.g., the surface facing the second mold component 240) is treated, typically before the first structure 202 is held in the first mold component 230, to facilitate coupling with the second structure 204. In some embodiments, the bottom surface of the first structure 202 is treated to reduce the hydrophobicity (e.g., increase the surface tension) of the first structure 202. In some embodiments, the bottom surface of the first structure 202 is roughened to increate the contact area with the second structure 204.
In some embodiments, the first mold component 230 has a flat surface or a portion of the surface that is flat facing the first structure 202. In some embodiments, the surface of the first mold component 230 has protrusions and/or indentations, the impact of which is described below with respect to
Once the heated plastic material is cooled, the plastic material forms the second structure 204. When the second structure 204 is formed, the second structure 204 is coupled with the first structure 202 so as to form the combination 220 of the first structure 202 and the second structure 204.
Note that the combination 220 removed from the first mold component 230 and the second mold component 240 has pin marks corresponding to the plurality of pins 242 coupled with the second mold component 240. When optical measurements (e.g., collection of optical images or optical signals) are performed through respective portions of the second structure 204 corresponding to the plurality of discrete through holes defined in the first structure 202, if the pin marks are located at the respective portions of the second structure 204 corresponding to the plurality of discrete through holes defined in the first structure 202, the pin marks interfere optical measurements. Thus, to avoid the interference by the pin marks, the plurality of pins 242 are located offset from the plurality of discrete through holes defined in the first structure 202. Alternatively, the first structure 202 and the second structure 204 are aligned so that the plurality of discrete through holes defined in the sheet layer of the first structure 202 is offset from the plurality of holding locations in the second structure 204.
Although
In some embodiments, the third structure 310 includes a plurality of vertical indentations 314 along the outside of the third structure 310. In some embodiments, a respective side of the third structure 310 defines a longitudinal axis, and respective vertical indentations 314 located on the respective side of the third structure 310 are substantially perpendicular to the longitudinal axis formed by the respective side of the third structure 310 (e.g., a respective vertical indentation 314 forms 60-120° with the longitudinal axis of the respective portion of the third structure 310). In some embodiments, the vertical indentations 314 are substantially perpendicular to the plane defined by the base layer 208 of the second structure 202 of the combination 220 (e.g., a respective vertical indentation 314 forms 45° or less with a surface normal of the base layer 208 of the second structure 202 of the combination 220). In some embodiments, the plurality of vertical indentations 314 reduces distortion of the third structure 310, thereby maintaining a flatness of the top surface of the third structure 310.
In some embodiments, the third structure 310 includes one or more handles 312, each handle 312 including a plurality of fins.
Once the second plastic material is cooled, the third structure 310 is formed. The third structure 310 is coupled with the combination 220 of the first structure 202 and the second structure 204. In some embodiments, the third structure 310 covers at least the one or more vertical structures of the second structure 204. In some embodiments, the third structure 310, when included, covers at least a portion of an inner surface of respective vertical structures 204, thereby forming one or more side walls. In other words, in such embodiments, the reservoir of the array plate 320 is defined by the third structure 310 on the sides, and the first structure 202 and the second structure 204 on the bottom. In some embodiments, a respective side wall of the one or more side walls has 1-8 mm, 2-5 mm, 2-4 mm, 2-3 mm, or 3-4 mm width. In some embodiments, a respective side wall of the one or more side walls has 1-10 mm, 2-9 mm, 3-8 mm, 4-7 mm, or 5-6 mm height.
In some embodiments, the one or more side walls each have an inner surface, an outer surface, a bottom adjacent the sheet layer of the first structure 202, and a top surface opposite the bottom, and a respective side wall of the one or more side walls includes one or more vertical indentations 314 (
In some embodiments, the one or more side walls are made of a hydrophobic material of a surface tension lower than 35 dynes/cm (e.g., hydrocarbon polymer, polypropylene, polytetrafluoroethylene, and their derivative, etc.). In some embodiments, the one or more side walls are made of a hydrophobic material of a surface tension lower than 25 dynes/cm.
In some embodiments, the one or more side walls each have an inner surface, an outer surface, a bottom adjacent the sheet layer of the first structure, and a top surface opposite the bottom, and the inner surface of a respective side wall of the one or more side walls is coated to expose a hydrophobic surface of a surface tension lower than 35 dynes/cm.
Array plates with the one or more side walls made with an elastic material can better handle thermal stress. Thus, in some embodiments, the hardness of the second plastic material is Shore A hardness of 85 or less. In some embodiments, the hardness of the second plastic material is Shore A hardness of 80 or less. In some embodiments, the hardness of the second plastic material is Shore A hardness of 75 or less. In some embodiments, the second plastic material has a tensile modulus of less than 2 GPa.
Although
Although
In some embodiments, the one or more vertical structures formed during the first molding process may be configured to form one or more side walls, thereby eliminating the need for a second molding process to form one or more side walls over the one or more vertical structures.
Alternatively, in some embodiments, the first structure 202 includes one or more vertical structures (e.g., the first structure 202 includes a tray that has the sheet layer and one or more vertical structures, such as short walls, along the periphery of the sheet layer). In such embodiments, the molding step to form the vertical structures is skipped. In a molding step for forming one or more side walls, the first structure 202 is placed inside a mold, and a heated plastic is introduced to form one or more side walls over the one or more vertical structures of the first structure.
When the inner side walls and the base layer form sharp corners (e.g., the inner side walls and the base layer form 90 degree angle), the sharp corners hold more residual wash solution due to increased surface interaction, i.e. adhesion between the plastic surface and the solution. Therefore, in some embodiments, the contact lines between the inner side walls and the base layer of the second structure have a curved transition (e.g., rounded) as shown in
In some embodiments, a mold surface that has indentations and/or protrusions is used. When the mold surface facing the top surface of the first structure 202 has indentations at locations corresponding to the plurality of discrete through holes defined in the first structure 202, the heated plastic material, when introduced into the cavity formed by mold components, fills the indentations. As a result, the top surface of the second structure is located above the top surface of the first structure as shown in
The method includes (602) providing a first structure. The first structure includes a sheet layer with a plurality of discrete through holes.
In some embodiments, the sheet layer includes (604) at least 50% of fluorocarbon by weight.
In some embodiments, the sheet layer includes (606) at least 90% of fluorocarbon by weight.
The method includes placing the first structure adjacent to a first surface of a mold. In some embodiments, the method includes (608) pressing the first structure against the first surface of the mold.
In some embodiments, includes placing the first structure adjacent to the first surface of the mold includes placing the first structure adjacent to the first surface of the mold with a plurality of pins. In some embodiments, pressing the first structure against the first surface of the mold includes pressing the first surface of the sheet layer against the first surface of the mold with a plurality of pins. In some embodiments, pressing the first structure against the first surface of the mold includes (610) pressing the first surface of the sheet layer against the first surface of the mold with a plurality of pins at least on the second surface of the sheet layer.
In some embodiments, the method includes (612) providing vacuum suction on the first surface of the sheet layer.
The method includes (614) providing a heated plastic material into the mold.
In some embodiments, the plastic material includes (616) polycarbonates.
In some embodiments, the plastic material includes (618) cyclic olefin polymer or copolymer.
The method includes cooling the plastic material to form a second structure. In some embodiments, the method includes (620,
In some embodiments, the plastic material of the second structure is (622) optically transparent.
In some embodiments, the method includes (624) coupling a third structure with at least the second structure over at least a portion of the one or more vertical structures, the third structure including one or more side walls.
In some embodiments, the one or more vertical structures of the second structure include (626) a plurality of pins vertically protruding from the rest of the one or more vertical structures.
In some embodiments, the method includes (628) molding the third structure over at least a portion of the one or more vertical structures with a second mold so as to couple the second structure and the third structure, and removing a combination of the second structure and the third structure from the second mold by pushing respective locations on the third structure that correspond to the plurality of pins of the second structure.
In some embodiments, the one or more side walls are (630) made of a plastic material that has a glass transition temperature lower than the glass transition temperature of (the material for) the second structure.
In some embodiments, the one or more vertical structures include (632) one or more side walls.
In some embodiments, the one or more side walls are (634,
In some embodiments, the one or more side walls each have (636) an inner surface, an outer surface, a bottom adjacent the sheet layer of the first structure, and a top surface opposite the bottom, and a respective side wall of the one or more side walls includes one or more lips on the top surface, at least one of the one or more lips aligned with the inner surface of the respective side wall.
In some embodiments, the one or more side walls each have (638) an inner surface, an outer surface, a bottom adjacent the sheet layer of the first structure, and a top surface opposite the bottom, and a respective side wall of the one or more side walls includes one or more vertical indentations along the outer surface of the respective side wall.
In some embodiments, the one or more side walls are (640) made of a hydrophobic material of a surface tension lower than 35 dynes/cm.
In some embodiments, the one or more side walls each have (642) an inner surface, an outer surface, a bottom adjacent the sheet layer of the first structure, and a top surface opposite the bottom, and the inner surface of a respective side wall of the one or more side walls is coated to expose a hydrophobic surface of a surface tension lower than 35 dynes/cm.
In some embodiments, the second structure includes (644) a plurality of holding locations, the method comprising aligning the first structure and the second structure so that the plurality of discrete through holes defined in the sheet layer of the first structure is offset from the plurality of holding locations in the second structure.
In some embodiments, the mold is configured (646,
In some embodiments, the mold is configured (648) so that a top surface of the sheet layer of the first structure is above a top surface of the base layer of the second structure.
In some embodiments, the mold is configured (650) so that a top surface of the sheet layer of the first structure is below a top surface of the base layer of the second structure.
In some embodiments, the first surface of the mold has (652) one or more of: a plurality of indentations and a plurality of protrusions corresponding to the plurality of discrete through holes defined in the sheet layer.
In some embodiments, at least one of the side walls includes (654) one or more handles, each handle comprising a plurality of parallel fins.
Many modifications and variations are possible in view of the above teachings. For example, in accordance with some embodiments, a method for making an array plate includes providing a first structure. The first structure including a sheet layer with a plurality of discrete through holes. The method includes pressing the first structure against a first surface of a mold, and providing a heated plastic material into the mold. The method includes cooling the plastic material to form a second structure so that the first structure and the second structure are coupled. The second structure includes a base layer and one or more side walls along a periphery of the base layer, adjacent a first surface of the base layer. At least a portion of a first surface of the sheet layer of the first structure is exposed from the third structure, and a second surface of the sheet layer, opposite to the first surface of the sheet layer, is embedded in the base layer of the second structure adjacent the first surface of the base layer.
In some embodiments, an array plate includes a first structure. The first structure including a sheet layer with a plurality of discrete through holes. The array plate also includes a second structure coupled to the first structure. The second structure including a base layer and one or more side walls along a periphery of the base layer, adjacent a first surface of the base layer. At least a portion of a first surface of the sheet layer of the first structure is exposed from the second structure, and a second surface of the sheet layer, opposite to the first surface of the sheet layer, is embedded in the base layer of the second structure adjacent the first surface of the base layer.
In accordance with some embodiments, a method for making an array plate includes providing a first structure. The first structure includes a sheet layer with a plurality of discrete through holes. The first structure also includes one or more vertical structures along a periphery of the sheet layer. The method includes pressing the first structure against a first surface of a mold, and providing a heated plastic material into the mold. The method includes cooling the plastic material to form a second structure so that the first structure and the second structure are coupled. The second structure includes a base layer and one or more side walls formed over the one or more vertical structures. At least a portion of a first surface of the sheet layer of the first structure is exposed from the third structure, and a second surface of the sheet layer, opposite to the first surface of the sheet layer, is embedded in the base layer of the second structure adjacent the first surface of the base layer.
In some embodiments, an array plate includes a first structure. The first structure including a sheet layer with a plurality of discrete through holes. The first structure also includes one or more vertical structures along a periphery of the sheet layer. The array plate also includes a second structure coupled to the first structure. The second structure including a base layer and one or more side walls formed over the one or more vertical structures. At least a portion of a first surface of the sheet layer of the first structure is exposed from the second structure, and a second surface of the sheet layer, opposite to the first surface of the sheet layer, is embedded in the base layer of the second structure adjacent the first surface of the base layer.
Operations and characteristics described above with respect to the method 600 are also applicable to these methods and apparatuses. For brevity, such operations and characteristics are not repeated herein.
In some embodiments, a method for using an array plate includes providing the array plate, wherein the array plate defines a reservoir. The method includes storing a liquid medium in the reservoir of the apparatus so that the first surface of the sheet layer is covered by the liquid medium, and dispensing respective liquid droplets on respective locations on the base layer. The respective locations correspond to locations of the plurality of discrete through holes defined in the sheet layer, and the respective liquid droplets are immiscible with the liquid medium.
In some embodiments, the method also includes adding one or more solutions to one or more liquid droplets of the respective liquid droplets.
In some embodiments, the method also includes performing an immunoassay by: immobilizing one of one or more antibodies and one or more antigens in one or more respective liquid droplets to the base layer, and adding one or more solutions to the one or more respective liquid droplets of the respective liquid droplets. At least one of the one or more solutions includes the other of the one or more antibodies and the one or more antigens. The method also includes detecting a binding of the at least one antigen with at least one antibody in the one or more respective liquid droplets.
In some embodiments, the method includes washing the respective liquid droplets on the apparatus by: removing a portion of the liquid medium, adding a wash buffer to the reservoir, shaking the apparatus so that the wash buffer and the respective liquid droplets are mixed, draining at least a portion of the wash buffer from the reservoir, and providing a liquid medium in the reservoir of the apparatus so that the first surface of the sheet layer is covered by the liquid medium.
The first structure 1210 includes a sheet layer 1212 that typically has a square or rectangular shape (e.g., a sheet of PTFE cut into a rectangle). Alternatively, the sheet layer of the first structure 1210 may have a round shape, such as a disc, or any other shape (e.g., a generally rectangular shape with one or more chamfered corners).
The sheet layer 1212 defines a plurality of discrete through-holes (e.g., 1214-1 through 1214-8). Typically, a discrete through-hole 1214 has a round shape (e.g., a circle or an oval). Alternatively, the discrete through-hole 1214 may have a non-round shape (e.g., a triangle, a square, a rectangle, a pentagon, a hexagon, an octagon, a star, a slit, etc.). In some embodiments, the plurality of discrete through-holes 206 are formed by punching holes through the sheet layer 1212. Typically, the plurality of discrete through-holes have substantially the same diameter (e.g., with less than 50, 30, 20, 10, or 5% variation among the holes). In some embodiments, a respective through-hole has a 1 mm-5 mm diameter, or 2 mm-3 mm diameter. In some embodiments, the discrete through-holes are arranged in a predefined pattern. For example, when 96 discrete through-holes are defined in the sheet layer 1212, the 96 discrete through-holes may be arranged in an 8×12 array. In another example, when 8 discrete through-holes are arranged in the sheet layer 1212, the 8 discrete through-holes may be arranged in a 2×4 array, as illustrated in
The second structure 1220 typically has a rectangular shape. For example, the second structure 1220 may have a shape and size of a microscope slide. However, the second structure 1220 may have a larger or smaller size than a microscope slide. In some embodiments, the second structure 1220 has a square shape. In some embodiments, the second structure 1220 has a non-rectangular shape (e.g., a disc or a generally rectangular shape with one or more chamfered corners).
In some embodiments, the sheet layer 1212 solely constitutes the first structure 1210. In some other embodiments, the first structure 1210 includes additional features, such as one or more vertical structures (e.g., the first structure 1210 may be a tray including the sheet layer and one or more sidewalls) in addition to the sheet layer 1212.
In some embodiments, the sheet layer 1212 of the first structure 1210 has a uniform thickness across the sheet layer 1212. In some other embodiments, the sheet layer 1212 has a range of thicknesses across the sheet layer 1212. Typically, the thickness of the sheet layer 1212 is less than the width and length of the sheet layer 1212. In some embodiments, the thickness of the sheet layer 1212 is less than a predefined thickness. For example, the sheet layer has a thickness typically of 0.01-10 mm, 0.1-2 mm, 0.2-1 mm, or 1-2 mm.
In some embodiments, the sheet layer 1212 is a sheet of a preselected material. The preselected material typically includes a polymer (e.g., polytetrafluoroethylene, any other perfluorocarbon polymer, or any other fluorocarbon polymer). In some embodiments, the sheet layer 1212 includes a sheet of a preselected material. For example, the sheet layer 1212 may include multiple layers of different materials, wherein one of the multiple layers (e.g., typically a top layer) is a sheet of fluorocarbon (e.g., polytetrafluoroethylene). Alternatively, the sheet layer 1212 may include a core (e.g., a sheet metal) coated with fluorocarbon (e.g., polytetrafluoroethylene).
In some embodiments, the sheet layer 1212 includes at least 50% of fluorocarbon by weight. Alternatively, the sheet layer 1212 may include at least 80, 90, 95, or 99% of fluorocarbon by weight. In some embodiments, the sheet layer 1212 includes at least 90% of polytetrafluoroethylene by weight. Alternatively, the sheet layer 1212 may include at least 50, 80, 95, or 99% of polytetrafluoroethylene by weight.
In some embodiments, a top portion of the sheet layer 1212 includes at least 95% of fluorocarbon by weight. As used herein, a top portion of the sheet layer 1212 refers to a layer that is defined by an exposed surface of the sheet layer 1212 and a predefined thickness. Thus, the top portion includes the exposed surface of the sheet layer 1212 and has the predefined thickness. In some embodiments, a top surface of the top portion is the exposed surface of the sheet layer 1212 and the bottom surface of the top portion has the same shape and size as the top surface of the top portion. In some embodiments, the exposed surface of the sheet layer 1212 has a flatness of at most 400 μm. In some embodiments, the bottom surface of the sheet layer 1212 has a flatness of at most 400 μm. In some embodiments, the thickness of the top portion may be 1 μm or 100 nm. In some embodiments, the top portion of the sheet layer 1212 includes at least 99% of fluorocarbon by weight.
In some embodiments, at least 90% of the exposed portion of the first surface of the first structure 1210 (e.g., the surface of the sheet layer 1212 that faces away from the second structure) is covered by fluorocarbon. In some embodiments, at least 95% of the exposed surface is covered by fluorocarbon. In some embodiments, at least 99% of the exposed portion of the first surface is covered by fluorocarbon. The PTFE-matrix does not satisfy this requirement because the resin is included in the exposed portion of the first surface. In some embodiments, at least 90% of the exposed portion of the first surface is covered by PTFE. In some embodiments, at least 95% of the exposed portion of the first surface is covered by PTFE. In some embodiments, at least 99% of the exposed portion of the first surface is covered by PTFE.
In some embodiments, the exposed portion of the first surface is characterized by advancing and receding contact angles, for a liquid selected from a group including water, ethanol, and isopropanol. The advancing and receding contact angles for the selected liquid on the exposed portion of the first surface are substantially similar to advancing and receding contact angles for the selected liquid on PTFE (e.g., a PTFE sheet containing at least 99% PTFE by weight). For example, the difference between the advancing contact angle for the selected liquid on the exposed portion of the first surface and the advancing contact angle for the selected liquid on PTFE is less than 20% or 10% of the advancing and receding contact angles for the selected liquid on PTFE.
In some embodiments, a first surface (e.g., a surface facing away from the second structure 1220) of the first structure 1210 is roughened to increase the hydrophobicity and/or oleophobicity.
In some embodiments, the second structure 1220 includes a plurality of structures that correspond to the plurality of discrete through-holes in the first structure 1210.
The second structure 1220 typically includes a plastic material. In some embodiments, the plastic material includes polycarbonates. In some embodiments, the plastic material includes cyclic olefin polymer or copolymer or polystyrene.
In some embodiments, the plastic material of the second structure 1220 is optically transparent. This allows the second structure 1220 to be optically imaged from a bottom surface side of the second structure 1220.
Although the sheet layer 1212 is illustrated as having a width less than the width of the second structure 1220 and a length less than the length of the second structure 1220 in
In some embodiments, a plurality of pins 1342 coupled with the second mold component 1340 are spring loaded so that the plurality of pins 1342 are configured to apply force on the first structure 1210 toward the first mold component 1330 when the first mold component 1330 and the second mold component 1340 are assembled together.
In some embodiments, the bottom surface of the first structure 1210 (e.g., the surface facing the second mold component 1340) is treated, typically before the first structure 1210 is held in the first mold component 1330, to facilitate coupling with the second structure 1220. In some embodiments, the bottom surface of the first structure 1210 is treated to reduce the hydrophobicity (e.g., increase the surface tension) of the first structure 1210. In some embodiments, the bottom surface of the first structure 1210 is roughened to increate the contact area with the second structure 1220.
In some embodiments, the first mold component 1330 has a flat surface or a portion of the surface that is flat facing the first structure 1210. In some embodiments, the surface of the first mold component 1330 has protrusions and/or indentations, the impact of which is described above with respect to
Once the heated plastic material is cooled, the plastic material forms the second structure 1220. When the second structure 1220 is formed, the second structure 1220 is coupled with the first structure 1210 so as to form the array slide 1200.
Note that the array slide 1200 removed from the first mold component 1330 and the second mold component 1340 has pin marks corresponding to the plurality of pins 1342 coupled with the second mold component 1340. When optical measurements (e.g., collection of optical images or optical signals) are performed through respective portions of the second structure 1220 corresponding to the plurality of discrete through-holes defined in the first structure 1210, if the pin marks are located at the respective portions of the second structure 1220 corresponding to the plurality of discrete through-holes defined in the first structure 1210, the pin marks interfere optical measurements. Thus, to avoid the interference by the pin marks, the plurality of pins 1342 are located offset from the plurality of discrete through-holes defined in the first structure 1210.
Although
The array slide 1400 has a first structure 1410 and a second structure 1420. The first structure 1410 includes a sheet layer 1412 and one or more connectors 1416. In some embodiments, the one or more connectors 1416 are integrated in the sheet layer 1412.
The first structure 1410 includes one or more connectors 1416. In some embodiments, at least one of the connectors 1416 is positioned so that its top surface is aligned with the top surface of the sheet layer 1412. However, as explained below with respect to
The one or more connectors 1416 serve multiple functions. For example, the one or more connectors 1416, in particular when the one or more connectors 1416 are embedded in the second structure 1420, prevents the peeling of the first structure 1410 from the second structure 1420. The one or more connectors 1416 also allow first structures for multiple array slides to be held together in the molding cavity. This facilitates the manufacturing of multiple array slides.
The array slide 1500 has a first structure 1510 and a second structure 1520. The first structure 1510 includes a sheet layer 1512 and one or more connectors (not shown). The sheet layer 1512 defines a plurality of discrete through-holes (1514-1 through 1514-8).
The first structure 1510 includes one or more connectors 1516. In
Although
Although
The method includes (702) providing a first structure in a mold (e.g.,
In some embodiments, the sheet layer includes (704) at least 50% of fluorocarbon by weight. In some embodiments, the sheet layer includes (706) at least 90% of fluorocarbon by weight. In some embodiments, the sheet layer includes (708) at least 95% of fluorocarbon by weight. In some embodiments, the sheet layer includes (710) at least 99% of fluorocarbon by weight.
In some embodiments, the sheet layer includes (712) at least 90% of polytetrafluoroethylene by weight. In some embodiments, the sheet layer includes (714) at least 95% of polytetrafluoroethylene by weight. In some embodiments, the sheet layer includes (716) at least 99% of polytetrafluoroethylene by weight.
In some embodiments, the method includes (718) pressing the first structure against a first surface of a mold prior to providing the heated plastic material (e.g.,
In some embodiments, pressing the first structure against the first surface of the mold includes (720) pressing the first surface of the sheet layer against the first surface of the mold with a plurality of pins at least on the second surface of the sheet layer (e.g.,
In some embodiments, the method includes (722) providing vacuum suction on the first surface of the sheet layer (e.g.,
The method includes (724) providing a heated plastic material into the mold (e.g.,
In some embodiments, the plastic material includes (726) polycarbonates.
In some embodiments, the plastic material includes (728) cyclic olefin polymer or copolymer or polystyrene.
In some embodiments, the plastic material is (730) optically transparent. In some embodiments, the plastic material is optically transparent for a wavelength range selected from the group consisting of: 250-900 nm, 35-850 nm, 400-800 m, 450-800 nm, and 500-800 nm.
The method includes (732) cooling the plastic material to form a second structure so that the first structure and the second structure are coupled (e.g.,
In some embodiments, a base of the second structure is (734) optically transparent. A base of the second structure includes one or more portions of the second structure located below the plurality of discrete through-holes defined by the first structure. In some embodiments, the base is optically transparent for a wavelength range selected from the group consisting of: 250-900 nm, 35-850 nm, 400-800 m, 450-800 nm, and 500-800 nm.
At least a portion of a first surface of the sheet layer of the first structure is exposed (736) from the second structure, and a second surface of the sheet layer, opposite to the first surface of the sheet layer, is embedded in the second structure (e.g.,
In some embodiments, a top portion of the sheet layer, including the exposed portion of the first surface of the sheet layer, includes (738) at least 95% of fluorocarbon by weight. In some embodiments, a top portion of the sheet layer, including the exposed portion of the first surface of the sheet layer, includes (740) at least 99% of fluorocarbon by weight.
In some embodiments, the top portion of the sheet layer is defined (742) by the exposed portion of the first surface and less than 1 μm thickness.
In some embodiments, the top portion of the sheet layer is defined (744) by the exposed portion of the first surface and less than 100 nm thickness.
In some embodiments, at least 90% of the exposed portion of the first surface is covered (746) by fluorocarbon. In some embodiments, at least 95% of the exposed portion of the first surface is covered (748) by fluorocarbon. In some embodiments, at least 99% of the exposed portion of the first surface is covered (750) by fluorocarbon.
In some embodiments, at least 90% of the exposed portion of the first surface is covered (752) by polytetrafluoroethylene. In some embodiments, at least 95% of the exposed portion of the first surface is covered (754) by polytetrafluoroethylene. In some embodiments, at least 99% of the exposed portion of the first surface is covered (756) by polytetrafluoroethylene.
In some embodiments, the exposed portion of the first surface is characterized (758) by advancing and receding contact angles, for a liquid selected from a group including water, ethanol, and isopropanol, that are similar to advancing and receding contact angles, for the selected liquid, on polytetrafluoroethylene.
In some embodiments, the second structure includes (760) a plurality of holding locations. The method includes aligning the first structure and the second structure so that the plurality of discrete through-holes defined in the sheet layer of the first structure is offset from the plurality of holding locations in the second structure.
In some embodiments, the mold is configured (762) so that a top surface of the sheet layer of the first structure is aligned with a top surface of a base layer of the second structure (e.g.,
In some embodiments, the mold is configured (764) so that a top surface of the sheet layer of the first structure is above a top surface of a base layer of the second structure (e.g.,
In some embodiments, at least a portion of the first surface of the sheet layer is embedded (770) in the second structure. For example, the second structure covers along a periphery of discrete through-holes defined by the sheet layer over the first surface of the sheet layer. In some embodiments, a plurality of portions of the first surface of the sheet layer is embedded in the second structure.
In some embodiments, the first structure includes (772) one or more connectors coupled to one or more sides of the sheet layer (e.g.,
In some embodiments, at least a portion of the sides of the sheet layer is angled (776) (e.g.,
In some embodiments, the second surface of the sheet layer has a larger area than the first surface of the sheet layer (780) (e.g.,
In some embodiments, the method includes (782) coating a portion of the second structure with oil. In some embodiments, the method includes coating (784) a portion of the first surface of the sheet layer of the first structure with the oil. In some embodiments, the oil is selected (786) from the group consisting of a mineral oil, a silicone oil, a hydrocarbon compound, a hydroperfluorocarbon compound and a perfluorocarbon compound.
In some embodiments, a method for using an array slide includes providing the array slide, and providing one or more biological and/or chemical samples for processing.
In some embodiments, a method for using an array slide includes placing the array slide in a reservoir. The method includes storing a liquid medium in the reservoir of the apparatus so that the first surface of the sheet layer is covered by the liquid medium, and dispensing respective liquid droplets on respective locations on the base layer. The respective locations correspond to locations of the plurality of discrete through-holes defined in the sheet layer, and the respective liquid droplets are immiscible with the liquid medium.
In some embodiments, a method includes processing a cell by placing a plurality of droplets on respective regions of the second structure that are not covered by the first structure. Respective droplets include cells for processing. The method also includes adding one or more biological and/or chemical reagents to the respective droplets.
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.
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.
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.
For example, in accordance with some embodiments, a device includes a first structure including a sheet layer with a plurality of discrete through-holes; and a second structure coupled to the first structure. The second structure includes a hydrophilic material. At least a portion of a first surface of the sheet layer of the first structure is exposed from the second structure. A top portion of the sheet layer, including the exposed portion of the first surface of the sheet layer, includes fluorocarbon. A second surface of the sheet layer, opposite to the first surface of the sheet layer, is embedded in the second structure. The second structure extends at least partially into the plurality of discrete through-holes of the first structure.
In accordance with some embodiments, a method includes providing a first structure in a mold, the first structure including a sheet layer with a plurality of discrete through-holes. The method also includes providing a heated plastic material into the mold, and cooling the plastic material to form a second structure so that the first structure and the second structure are coupled. At least a portion of a first surface of the sheet layer of the first structure is exposed from the second structure. A top portion of the sheet layer, including the exposed portion of the first surface of the sheet layer, includes fluorocarbon. The second structure includes a material of a higher surface tension than the top of the sheet layer (e.g., a hydrophilic material). A second surface of the sheet layer, opposite to the first surface of the sheet layer, is embedded in the second structure. The second structure extends at least partially into the plurality of discrete through-holes of the first structure.
This application is a divisional application of U.S. patent application Ser. No. 14/452,172, filed Aug. 5, 2014, which is a continuation-in-part application of PCT Patent Application Serial No. PCT/IB2013/000623 filed on Feb. 5, 2013, which claims the benefit of and priority to U.S. Provisional Patent Application Ser. No. 61/595,131, filed on Feb. 5, 2012 and U.S. Provisional Patent Application Ser. No. 61/711,127, filed on Oct. 8, 2012, all of which are hereby incorporated by reference in their entireties.
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| Number | Date | Country | |
|---|---|---|---|
| 20180229233 A1 | Aug 2018 | US |
| Number | Date | Country | |
|---|---|---|---|
| 61711127 | Oct 2012 | US | |
| 61595131 | Feb 2012 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 14452172 | Aug 2014 | US |
| Child | 15950580 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | PCT/IB2013/000623 | Feb 2013 | US |
| Child | 14452172 | US |
