Cap for analytical instrument

Abstract

The present invention provides an analytical instrument designed to protect the aqueous solution in each well from contamination and / or evaporation. [Solution] An analytical apparatus comprising an analytical apparatus component and a biocompatible, removable cap fitted to the analytical apparatus component. The top surface of the analytical apparatus component includes at least one row having a plurality of wells. Each well is defined by a well bed, a well diameter, and a well height. The top surface of the analytical apparatus component includes the top surfaces of the plurality of wells. A platform having the top surface extends over each side of the at least one row and terminates at the proximal and distal ends of the analytical apparatus component. Each of the at least one row is recessed from the top surface of the platform, thereby defining a recess present beneath the top of the platform. The bottom of the recess includes the top surface of the analytical apparatus component.

Description

Technical Field

[0001] The present disclosure provides an apparatus and method for performing analysis for combinatorial libraries. The apparatus includes a number of wells and removable caps. When the wells contain an aqueous analysis solution, the caps protect the solution from contamination. In addition, the caps described herein create a fluid pathway across the top of the wells within the analyzer, thereby allowing placement of a layer of hydrophobic fluid across the wells and the top surface of the apparatus. This fluid layer prevents evaporation of moisture from the aqueous solution within the wells and discourages entry of contaminants into these wells.

Background Art

[0002] Combinatorial libraries are well known in the literature and often utilize beads, where each bead contains multiple copies of a single compound attached to the bead by a linker. In addition, typically, the beads contain a reporter element such as DNA that allows analysis of the structure of the single compound on the bead. Many of these libraries are limited by the fact that the compounds being tested remain on the bead during analysis. As such, the biological data generated by the analysis is potentially wasted due to the possibility that the bound compound may not bind effectively to the optimal target. This could be due to physical interference from the bead, as well as possible steric interference by the linker connecting the compound to the bead. In the latter case, this linkage may either inhibit the ability of an effective compound to bind properly to the target, thereby providing an analysis result that is less well evidenced than the actual effectiveness of the compound.

[0003] One option to address this problem is the use of a cleavable linker that cleaves under appropriate stimulation (e.g., light), thereby releasing the compound from the bead. Once the compound enters a solution, such as in a test well, it is free and adapts itself to provide maximum efficacy in analysis. Furthermore, the release of these compounds can be carried out in such a way that the amount of compound released is controlled in order to provide meaningful dose-dependent data. See, for example, U.S. Patent Application No. 2019-0358629, which is incorporated entirely herein by reference. [Overview of the project] [Problems that the invention aims to solve]

[0004] It is generally desirable for an analysis to include as many test compounds as possible. However, the number of individual compounds that can be tested in a single analysis is generally limited by the number of wells on the analytical instrument. Increasing the number of individual wells to accommodate a larger library introduces further problems. If adjacent wells are too close together, some of the solution in one well may spill out and contaminate the solution in the adjacent well. Any spillage from one well to an adjacent well will contaminate the adjacent well. Such contamination can alter the results by resulting in either a false affirmation or dilution of the reported activity of the active compound. The former can occur when the test compound in solution is active in the first well, and some of its solution "spilles" into an adjacent well containing an inactive compound. As a result, the adjacent well now contains the active compound in its solution, leading to a false report that the solution in that well has activity. The latter can occur when spillage from a well containing an inactive compound contaminates an adjacent well containing an active compound, thereby reducing the concentration of the active compound, so that the reported activity, when reported in a dose-dependent manner, is less than the actual activity.

[0005] This spillage problem becomes particularly real when analytical instruments have a large number of wells that are close together. To maintain a workable size for the instrument, the well density is increased to the point where the aqueous solution in one well can spill and contaminate adjacent wells. At this density, the reliability of the analysis decreases due to the decreasing reliability that increases with cell density. This presents a difficult situation for engineers. In one case, an analytical instrument with wells spaced so far apart that the instrument cannot accommodate any more wells (e.g., a well density that is too low) is usable. In another case, an analytical instrument designed to account for spillage is usable.

[0006] One solution to this problem is described in U.S. Patent Application No. 16-774871, titled "Assay Devices for Combinatorial Libraries." However, further improvements are needed, as described below.

[0007] Furthermore, in order to accommodate a very large number of wells on a single apparatus, the volume of each well must be extremely small. For example, a well with a diameter of approximately 150 microns and a depth of 150 microns, when partially filled to about 40% of its capacity, contains approximately 0.001 milliliters of aqueous solution. Such small amounts of fluid require protection against contamination of the well (e.g., by contamination via air) and to prevent evaporation of water from the well. The latter is particularly practical when performing concentration-dependent analyses, where any evaporation of water from a particular well would change the concentration of the compound in that well.

[0008] Including fixed or permanent caps spanning the wells within the analyzer makes it difficult or impossible to add analytical components (e.g., beads, aqueous solutions, targets, etc.) to each well. Furthermore, temporary caps that fit over the top surface of the analyzer can lead to spillage if the cap is removed due to any suction to the instrument.

[0009] Thus, there is a current need for analytical instruments designed to protect the aqueous solutions in each well from contamination and / or evaporation, so that the results of the analysis performed in each well are reliable. Such instruments represent essential equipment in the art. [Means for solving the problem]

[0010] In one embodiment, the disclosure provides an analytical apparatus (1) including a well (10), the analytical apparatus including a removable cap (30) that is adjacent to but not in contact with the upper surface of the well (10). The cap (30) is configured to create a sealed fluid passage (5) over the well (10) that protects against contamination and / or evaporation.

[0011] In one embodiment, the present disclosure provides an analytical apparatus (1), which is: i) An analytical instrument component (1a) having at least one row (20) of wells (10) defined by a well bed (12), a well diameter (14), and a well height (15), wherein each first well (10a) is separated from an adjacent second well (10b) by a partition (16), The analytical apparatus component (1a) terminates on the upper surface (2) which includes the surface partition (16) and the top of the well (10), ii) To retract the row (20) from its upper surface, a platform (7) is provided that extends over at least a portion of the surface (2) of the analytical instrument component (1a), but does not extend over the row (20), iii) Each row (20) having one end terminated at an inlet port (3a) and the other end terminated at an outlet port (4a), The analyzer component (1a) and platform (7) are configured to receive and maintain the biocompatible removable cap (30). The cap (30) includes a bottom surface (31), and the configuration of the analyzer component (1a), platform (7), inlet (3a), outlet (4a), and the bottom surface (31) of the cap (30) isolates the row (20), thereby allowing the cap (30) to be maintained on the platform (7) to define a sealed fluid passage (5) extending from the inlet port (3a) to the outlet port (4a) through a space defined by the top surface (2) of the analyzer component (1a), the platform (7), and the bottom surface (31) of the cap (30), the height of the space being defined by the height of the platform (7). The sealed passage (5) provides the fluid communication in a substantially horizontal direction with respect to the top of the well (10).

[0012] In one embodiment, the present disclosure provides a kit of parts, which includes, A) Analytical apparatus (1), i) An analytical instrument component (1a) having at least one row (20) of wells (10) defined by a well bed (12), a well diameter (14), and a well height (15), wherein each first well (10a) is separated from an adjacent second well (10b) by a partition (16), An analytical instrument component (1a) terminates on the upper surface (2) which includes the surface of the partition (16) and the top of the well (10), ii) To retract the row (20) from its upper surface, a platform (7) is provided that extends over at least a portion of the surface (2) of the analytical instrument component (1a), but does not extend over the row (20), iii) Each row (20) having one end terminated at an inlet port (3a) and the other end terminated at an outlet port (4a), The analyzer component (1a) and platform (7) are configured to receive and maintain a removable biocompatible cap (30) in the analyzer, B) A removable biocompatible cap (30) including a bottom surface (31), The configuration of the analyzer component (1a), platform (7), inlet (3a), outlet (4a), and bottom surface (31) of the cap (30) isolates the row (20), thereby allowing the cap (30) to be maintained on the platform (7) to define a sealed fluid passage (5) extending from the inlet port (3a) to the outlet port (4a) through the space defined by the top surface (2) of the analyzer component (1a), the platform (7), and the bottom surface (31) of the cap (30), the height of the space is defined by the height of the platform membrane (7a). A kit of components, including a removable biocompatible cap (30) that provides the fluid communication substantially horizontally with respect to the top of the well (10) through a passage (5).

[0013] In one embodiment, the row (20) of the analyzer (1) includes high-density wells (10) aligned thereon, and each of the wells (10) is a) Floor (12) and height (15) that define the diameter (14) and depth (15) configured to hold the analysis component (60), b) A partition (16) that separates any two adjacent wells (10a) and (10b) from each other, each having a length of at least about 10 microns from the nearest edge of the first well (10a) to the nearest edge of the second well (10b), wherein the second well (10b) is the nearest adjacent well from the first well (10a), and the partition (16) is the partition (16).

[0014] In one embodiment, each of the partitions (16) of the apparatus (1) includes a hydrophobic water-repellent layer incorporated on at least a portion of the surface (2) on the partition (16).

[0015] In one embodiment, the row (20) has a well (10) density of at least 10 wells per square millimeter.

[0016] In one embodiment, the cap (30) covers the column (20) and, together with the platform (7), isolates the column (20) within a sealed conduit on the surface (2) of the analysis component (1a).

[0017] In one embodiment, the analyzer (1) includes a single column and a single pair of an inlet tank (3) / inlet port (3a) and an outlet tank (4) / outlet port (4a).

[0018] In one embodiment, the analyzer (1) includes a plurality of columns (20) and a plurality of pairs of an inlet tank (3) / inlet port (3a) and an outlet tank (4) / outlet port (4a), and each pair is aligned with each column (20).

[0019] In one embodiment, the platform (7) is incorporated on a part of the upper surface of the analyzer component (1a) and extends sufficiently upward such that the top of the platform (7) is higher than the inlet port (3a) and the outlet port (4a). In one embodiment, the inlet port (3a) is in fluid communication with the inlet tank, and the outlet port (4a) is in fluid communication with the outlet tank.

[0020] In one embodiment, the platform (7) is incorporated on the bottom surface of the cap (30) and extends sufficiently downward such that the bottom surface (31) of the cap (30) is higher than the inlet port (3a) and the outlet port (4a) but below the tops of the inlet tank (3) and the outlet tank (4).

[0021] In one embodiment, the platform (7) is a platform film (7a) that retracts the column (20) under the platform film (7a), thereby covering that portion of the surface (2) other than the column (20) to isolate the column (20). In this embodiment, the column (20) is now retracted relative to the film (7a).

[0022] In one embodiment, the platform (7) is a pair of shoulders (7b) positioned adjacent to each side of the row (20) and extending from an inlet port (3a) to an outlet port (4a) in order to retract the row (20) below the shoulders (7b).

[0023] In one embodiment, the platform (7) is a series of shoulders (7b) placed around the surface (2) to retract the row (20) below the shoulders (7b).

[0024] In each of the above embodiments, the platform (7) places the bottom (31) of the cap (30) relative to the surface (2) of the analyzer component (1a) such that the bottom (31) of the cap is above the inlet port (3a) and outlet port (4a) but below the inlet (3) and outlet (4) so ​​that a sealed passage (5) is formed when the cap (30) is positioned on the platform (7). The sealed passage extends from the inlet port (3a) through the platform (7), the row (20), the cap (30), and the space defined by the outlet port (4a).

[0025] In one embodiment, the analyzer (1) includes 10,000 to 2,500,000 wells (10).

[0026] In one embodiment, the analyzer (1) includes a single column (20).

[0027] In one embodiment, the analyzer (1) preferably includes a number of rows (20) that are aligned in parallel.

[0028] In one embodiment, the analytical device (1) is A) Analytical apparatus (1), i) An analytical instrument component (1a) having at least one row (20) of wells (10) defined by a well bed (12), a well diameter (14), and a well height (15), wherein each first well (10a) is separated from an adjacent second well (10b) by a partition (16), An analytical instrument component (1a) terminates on the upper surface (2) which includes the surface of the partition (16) and the top of the well (10), ii) To retract the row (20) from its upper surface, a platform (7) is provided that extends over at least a portion of the surface (2) of the analytical instrument component (1a), but does not extend over the row (20), iii) Each row (20) having one end terminated at an inlet port (3a) and the other end terminated at an outlet port (4a), The apparatus component (1b) is configured to receive and maintain a biocompatible removable cap (30) in an analyzer (1), B) A removable biocompatible cap (30) having a bottom surface (31), The configuration of the analyzer component (1a), platform (7), inlet (3a), outlet (4a), and bottom surface (31) of the cap (30) isolates the row (2), thereby allowing the cap (30) to be maintained on the platform (7) to define a sealed fluid passage (5) extending from the inlet port (3a) to the outlet port (4a) through a sealed space defined by the top surface (2) of the analyzer component (1a), the platform (7), and the bottom surface (31) of the cap (30), the height of the space being defined by the height of the platform (7). The sealed fluid passage (5) includes a cap (30) that provides the fluid communication substantially horizontally with respect to the top of the well (10), C) The well (10) in the analyzer (1) contains sufficient analytical components (60) for performing the analysis.

[0029] In one embodiment, the intake tank (3) is a syringe or pipette containing a desired fluid, and the outlet tip of the syringe or pipette combines with the intake port (3a), which, when combined, allows the fluid to be introduced into the passage (5).

[0030] In one embodiment, the intake tank (3) is a needle connected to a pump containing a desired fluid. The needle combines with the intake port (3a) to enable the pump to continuously deliver the fluid into the passage (5) under controlled pressure and delivery rate.

[0031] In one illustrated embodiment, the intake tank (3) is a well fixed in a predetermined position over the intake port (3a), and the well is in fluid communication with the intake port (3a) such that the fluid in the intake tank (3) flows to it through the intake port (3a) and through the passage (5).

[0032] In one embodiment, the fluid outlet (4) is an overflow outlet from the outlet port (4a), and any fluid exceeding the volume capacity of the passage (5) flows out from (4a).

[0033] In one illustrated embodiment, the fluid outlet (4a) is a well fixed in a predetermined position over the outlet port (4a), and the well is in fluid communication with the outlet port (4a) such that any fluid exceeding the volume capacity of the passage (3) flows out from the outlet port (4a) into the fluid outlet (4).

[0034] An analytical apparatus is provided. This analytical apparatus may include a) an analytical apparatus component having a top surface, and b) a biocompatible, removable cap having a bottom surface that fits therein. The top surface of the analytical apparatus component may include at least one row having a plurality of wells. Each of the plurality of wells may be defined by a well bed, a well diameter, and a well height. The top surface of the analytical apparatus component may include the top surfaces of the plurality of wells.

[0035] The analyzer may include a platform having a top surface that extends over each side of at least one row and terminates at the proximal and distal ends of the analyzer components, but does not extend over at least one row, thereby setting back each of at least one row from the top surface of the platform, thereby defining a recess located beneath the top of the platform. The bottom of the recess may include the top surface of the analyzer components.

[0036] The biocompatible removable cap may be fitted onto the platform of the analytical instrument component, thereby isolating a recess. This recess may terminate at one end with an intake tank / intake port and at the other end with an outlet tank / outtake port.

[0037] The recess, along with the bottom surface of the platform and the biocompatible removable cap, may define a sealed passage or conduit from the intake tank / intake port to the outlet tank / outlet port.

[0038] The sealed passage or conduit may provide a substantially horizontal fluid communication with respect to the top of the well.

[0039] The apparatus may include a single row and a single pair of inlet tanks / inlet ports and outlet tanks / outlet ports. The inlet tanks may be in fluid communication with the inlet ports, and the outlet tanks may be in fluid communication with the outlet ports.

[0040] The apparatus may include a number of rows and a number of pairs of intake tanks / intake ports and outlet tanks / outlet ports. Each pair may be aligned with each row. Each intake port may be in fluid communication with an intake tank, and each outlet port may be in fluid communication with an outlet tank.

[0041] The platform may be integrated onto a portion of the top surface of the analytical instrument component and extend sufficiently upward so that the top surface of the platform is higher than the intake and outlet ports.

[0042] The intake port may be in fluid communication with the intake tank, and the outlet port is in fluid communication with the outlet tank.

[0043] The platform may be incorporated on the bottom surface of the biocompatible removable cap and may extend sufficiently downward so that the bottom surface of the biocompatible removable cap does not become lower than the inlet and outlet ports.

[0044] The platform may be a membrane placed over portions of the surface other than the at least one row in order to recede at least one row beneath the platform membrane and thereby isolate at least one row.

[0045] The platform may be a pair of shoulders extending from an inlet port to an outlet port, mounted adjacent to each side of at least one row to recede at least one row below the shoulders.

[0046] The platform may be a series of shoulders placed around the upper surface of the analyzer to retract at least one row below the shoulders.

[0047] The apparatus may include 10,000 to 2,500,000 wells.

[0048] A fluid outlet may be provided for overflow from the outlet port. Fluid exceeding the volumetric capacity of the sealed passage or conduit may flow out from the outlet port.

[0049] The fluid outlet may be a well fixed in a predetermined position across the outlet port. The well may be in fluid communication with the outlet port so that fluid exceeding the volume capacity of a sealed passage or conduit flows out of the outlet port into the fluid outlet.

[0050] An analytical apparatus is provided. This analytical apparatus may include a) an analytical apparatus component having a top surface, and b) a biocompatible, removable cap fitting thereto and having a bottom surface. The top surface of the analytical apparatus component may include at least one row having a plurality of wells. Each of the plurality of wells may be defined by a well bed, a well diameter, and a well height. The top surface of the analytical apparatus component may include the top surfaces of the plurality of wells.

[0051] The analyzer may include a platform. The platform may have a top surface that extends over each side of at least one row and terminates at the proximal and distal ends of the analyzer components, but does not extend over at least one row, thereby setting back each of at least one row from the top surface of the platform, thereby defining a recess located beneath the top of the platform. The bottom of the recess may include the top surface of the analyzer components.

[0052] The configuration of the analytical instrument components, platform, intake tank / intake port, outlet tank / outtake port, and bottom surface of the removable biocompatible cap may allow the removable biocompatible cap to fit onto the platform to isolate the recess. The recess may terminate at one end in the intake tank / intake port and at the other end in the outlet tank / outtake port.

[0053] The recess, along with the bottom surface of the platform and the biocompatible removable cap, may define a sealed passage or conduit from the intake tank / intake port to the outlet tank / outlet port.

[0054] The removable biocompatible cap may be placed on or removed from the analytical instrument component.

[0055] A sealed passage or conduit may provide a substantially horizontal fluid communication with respect to the top of the well. [Brief explanation of the drawing]

[0056] [Figure 1A] This is a cross-sectional view of the analytical instrument (1) that defines a sealed fluid passage (5) when used in conjunction with the cap (30). [Figure 1B] This is an exploded view of an analytical instrument (1) showing several embodiments of the instrument, including the use of a platform membrane (7a), which is a thin layer or a separated sheet including an intake port (3a) and an outlet port (4a). [Figure 2] This figure shows a row (20) of analyzers (1) having a fluid inlet (3) / fluid inlet port (3a) and a fluid outlet (4) / fluid outlet port (4a - shown in Figure 1B), with shoulders (7b) resting on the periphery of the surface of the analyzer component (1a). [Figure 3] This figure shows a row (20) of analyzers (1) having a fluid inlet (3) / fluid inlet port (3a) and a fluid outlet (4) / fluid outlet port (4a - shown in Figure 1B), with shoulders (7b) resting on the periphery of the surface of the analyzer component (1a). [Figure 4] This figure shows a portion of column (20) containing wells (10), (10a), and (10b). [Figure 5A] This figure shows the removable caps (30) arranged across the top surface (2) of the remaining part of the analyzer (1). [Figure 5B] This figure shows a removable cap placed on the top surface (2) of the remaining part of the analytical device (1). [Modes for carrying out the invention]

[0057] The fluid inlet (3) and fluid outlet (4) are optional, self-supporting components fixed to the upper surface of the sheet, providing a fluid conduit that enters through the inlet port (3a) via the passage (5) from the fluid inlet (3) and exits through the outlet port (4a) and the fluid outlet (4).

[0058] Referring to Figure 1A, a cross-section of one embodiment of the apparatus (1) is shown. The apparatus (1) includes an analytical instrument component (1a), which includes a plurality of wells (10) configured to hold individual analytical components (60) which may be beads, cells, or a combination thereof. The analytical instrument (1) also features a removable cap (30), which may be mounted on the apparatus (1) or provided unmounted. When mounted on the apparatus (1), the cap (30) rests on a platform (7), in which position it creates a sealed fluid passage (5) constrained by the top surface of the analytical instrument component (1a), the bottom surface of the cap (30), and the wall surface of the platform (7). The sealed fluid passage (5) communicates with a fluid inlet (3) via an intake port (3a) that allows for the introduction of a fluid (typically oil less dense than water) to cover (and thereby protect) the contents of the wells (10) and fill the sealed fluid passage (5). The design of introducing fluid via the analyzer (1) allows for a sealed fluid passage (5) to be filled by a horizontal flow of fluid, avoiding obstruction of the contents of the wells (10) and preventing splashing of contents from one well to the next. The outlet port (4a, see, for example, Figure 1B) is located distal to the inlet port (3a). The outlet port (4a) allows the user to visually determine when the sealed fluid passage (5) is completely filled, to the point where excess fluid emerges from the port (4a). Finally, the platform (7) may be integrated with the analyzer component (1a), allowing the cap (30) to be placed on the platform (7), or the platform (7) may be integrated with the cap (30), allowing the platform (7) to be placed on the surface of the analyzer component (1a). However, before describing the present invention in more detail, the following terms are first defined. Unless otherwise defined, terms used herein have their generally accepted scientific meanings.

[0059] For ease of reference, many of the devices and numbers used herein are summarized below.

[0060] <Analyzer> The analytical apparatus (1) includes an analytical apparatus component (1a) whose upper surface (2) has one or more rows (20), each of which contains a number of wells (10) in which the analysis is performed. Any of the numbers (1) to (7b) described herein correspond to elements of the analytical apparatus (1) other than the wells (10), as follows: Analyzer (1) Analytical instrument component (with well) (1a) Device component (1b) (combination of 1a and 7a) Top view of the analytical instrument component (2) Fluid inlet or inlet tank (3) Fluid intake port (3a) (4) Fluid outlet or outlet tank Fluid outlet port (4a) Closed fluid passage (5) Platform (7) Platform membrane (7a) Shoulder (7b)

[0061] <Well> The wells (10) are found on the upper surface (2) of the analytical instrument component (1a). The wells (10) are arranged on the upper surface (2) in any suitable manner, including over part or all of the upper surface (2). Any number in the range (10) to (19) described herein corresponds to an element of well (10) as follows: Well (10) First well (10a) The second well (the nearest adjacent well) (10b) well surface (11) Well floor (12) Well diameter (14) Well height (15) Well partition (16) Water-repellent layer (22) Partition surface (19)

[0062] <column> A column (20) contains wells (10). These wells (10) are preferably arranged in one or more columns (20) on the upper surface (2) of the analyzer (1). They can be a single column (20) or a number of separate columns (20), the latter preferably arranged in parallel. Any number in the range (20) to (29) described herein corresponds to an element of column (20) as follows: Column (20) Column surface (21) Water-repellent layer (not shown) Hydrophobic fluid layer (not shown)

[0063] <Cap> The cap (30) has a bottom surface (31), and its dimensions are such that the cap (30) is located above the surface (2) of the analyzer (1), the fluid inlet port (3a), and the fluid outlet port (4a), thereby enabling the sealing fluid passage (5) described herein. Any number in the range (30) to (31) described herein corresponds to an element of the well (10) as follows: Cap (30) Bottom of the cap (31) Top of the cap (opposite side of 31)

[0064] <Bead> The bead contains multiple copies of the same compound and can be magnetic or nonmagnetic, having a diameter and height. If the bead is spherical, its diameter and height are identical.

[0065] <cell> The cells include mammalian cells such as mouse cells, pig cells, and primate cells (including human cells). The cells are available for use in the analytical instrument (1) to evaluate the biological activity of the test compound.

[0066] <Analysis Components> The analytical component (60) refers to any component used in the well (10) to perform the analysis. In one embodiment, the analytical component (60) is one or more of the following: beads, cells including human cells such as HeLa cells, buffers, salts, nutrients, water, reporter molecules, DNA, RNA, etc. Any of the features mentioned below corresponds to the analytical component (60) as follows. Analysis components (60) Target (not shown)

[0067] The technical terms used herein are for the purpose of describing only specific embodiments and are not intended to limit the invention. As used herein, the singular forms "a," "an," and "the" are also intended to include the plural forms unless the context clearly indicates otherwise.

[0068] "Optional" or "optionally" means that the event or situation described that follows may or may not occur, and that the description includes instances in which the event or situation may occur and instances in which it may not occur.

[0069] For example, when used before a numerical specification, including a range, for temperature, time, quantity, concentration, or other values, the term "about" indicates an approximate value that may vary by only + or - 10%, 5%, or 1%, or a partial range or lower value between them. Preferably, when used in relation to a quantity, the term "about" means that the quantity may vary by + / - 10%.

[0070] "Comprising" or "comprises" is intended to mean that the composition and method described include the elements but do not exclude other elements.

[0071] "Consisting essentially of," when used to define a composition or method, means excluding other elements that have some essential importance to the combination for the stated purpose. Therefore, a composition that is essential to the elements defined herein does not exclude other substances or processes that do not substantially affect the basic and novel properties of the claimed invention.

[0072] "Consisting of" means excluding more trace elements of other contaminants and more substantial steps of the method than are otherwise present. Embodiments defined by each of these conversion terms are within the scope of the present invention.

[0073] The term "assay device" refers to an apparatus capable of simultaneously analyzing a large number of test compounds against a target. This apparatus includes numerous wells, each containing, preferably, multiple copies of a compound that are substantially identical. The apparatus contains a vast number of wells. In one embodiment, the number of wells ranges from approximately 5,000 to approximately 2,000,000. In one embodiment, the density of wells on the apparatus is at least 10 wells per square millimeter, and the number of wells is at least approximately 5,000.

[0074] The term "assay component" refers to a component that is necessary for performing a specific analysis. Analytical components include, but are not limited to, water, salt, buffers, beads, cells, nutrients, test compounds, and marker compounds.

[0075] The term "bead" refers to a bead that is well known in the art for use in combinatorial chemistry. In one embodiment, the surface of the bead contains a number of identical test compounds bonded to this surface via cleavable linkers. The bead may also include DNA barcodes that record the structure of the test compound or the synthesis steps used to synthesize the compound. These barcodes are attached to the bead by either cleavable or non-cleavable linkers. If the barcodes are attached via cleavable linkers, preferably the cleavable linkers used with the barcodes are cleaved by a mechanism different from that of the test compound.

[0076] In other embodiments, the bead contains multiple copies of the same reporter molecule, either on the same bead to which multiple copies of the test compound are bound, or on separate beads. An example of a reporter molecule is a fluorescent molecule bound to the bead via a cleavable linker. Preferably, the reporter molecule is attached using the same cleavable linker used to bind the test compound to the bead. When used in this manner, the bead may contain a quenching molecule bound close to the fluorescent molecule on the bead to reduce the resulting fluorescence. Preferably, this quenching molecule is bound to the bead by either an incleavable bond or a cleavable bond that is preferably cleaved by a mechanism different from the cleavable linker used to bind the fluorescent molecule to the bead. During analysis, knowledge of the extent to which the test compound is released from the bead by a stimulus that cleaves the cleavable bond may be essential to the analysis. The use of a bead equipped with a reporter molecule can provide knowledge by measuring the change in fluorescence on a calibration curve resulting from the release of the fluorescent compound from the bead, away from the quenching material. For example, see U.S. Patent Application No. 2019-0358629, filed August 7, 2019, entitled “Oligonucleotide Encoded Chemical Libraries,” which is incorporated in its entirety herein by reference.

[0077] Beads are typically polymerized in form, although some of them contain enough Fe3O4 to make themselves magnetically sensitive. Many beads are commercially available in various sizes, ranging from approximately 0.1 microns to over 10 microns, and include amino-functionalized beads, carboxyl-functionalized beads, and magnetic beads with functional groups. See, for example, Spherotech Inc., Lake Forest, Illinois, USA, and Agilent Inc., Santa Clara, California, USA. These beads are immediately functionalized to contain test compounds and / or reporter molecules using conventional chemistry well known in the art. It will be understood that a bead with a nominal diameter of 5 microns includes beads smaller than and larger than 5 microns, with a number mean of 5 microns. To avoid the placement of numerous beads in a single well (10), smaller beads can be excluded by size exclusion filtration using a filter that allows beads smaller than a set diameter to pass through while collecting beads larger than this diameter. Thus, in one embodiment, a 5-micron bead size refers to beads filtered to remove substantially all beads smaller than 5 microns. Such beads are referred to herein as “size exclusion beads.” In all cases described herein, size exclusion beads represent a preferred subgroup of beads. The size, including the endpoints, may be any value or partial range within the described range.

[0078] In one embodiment, the analytical component is a growable mammalian cell (60), such as a human cell. This cell is used in the analysis to evaluate the biological activity, if present, of a specific test compound. Analysis using mammalian cells is well known in the art. Suitable cells include cancer cells, beta cells responsible for insulin expression, neurons, and the like.

[0079] The term "test compound" refers to a compound that is releasedly bound to the bead and, once released, is tested for biological activity in an analysis performed in the well (10) of the analytical instrument (1).

[0080] The term “releasably bound” means that the test compound bound to the bead can be released by applying a stimulus that breaks the bond. Such bonds are sometimes referred to herein as “cleavable” bonds. There are many examples in the art of cleavable bonds and suitable stimuli to break these bonds. Non-exclusive examples of cleavable bonds include those released by changes in pH, enzymatic activity, oxidative changes, redox reactions, ultraviolet light, infrared light, ultrasound, and changes in magnetic fields. A comprehensive overview of such cleavable bonds and the corresponding stimuli required to break them is provided in Taresco et al., “Self-Responsive Prodrug Chemistries for Drug Delivery,” Wiley Online Library, 2018, onlinelibrary.wiley.com / doi / full / 10.1002 / adtp.201800030, which is incorporated herein by reference in its entirety.

[0081] The term "platform" refers to a film or layer that is fixed to and extends over a portion of the upper surface (2) of the analytical instrument component (1a), other than the row (20) which is set back relative to the platform (7). The platform (7) is preferably a biocompatible material such as a polymer (e.g., plastic) that is insoluble in both water and hydrophobic fluids.

[0082] The term "hydrophobic fluid" refers to a biocompatible liquid that is insoluble in water and has a density lower than that of water. Examples of hydrophobic fluids include silicone oil and mineral oil.

[0083] <Analyzer> Moving on to the analyzer (1), Figure 1B shows one embodiment of the analyzer (1) having a number of rows (20) of wells (10—shown in Figures 1A and 4). Each row (20) is connected at its proximal end to an inlet port (3a) that connects to an inlet tank (3), and at its distal end to an outlet port (4a) and an outlet tank (4). The inlet port (3a) and outlet port (4a) are shown as separate layers containing holes for measuring the flow rate of fluid from the outlet tank (3) to the outlet tank (4). In some embodiments, the platform is a layer or membrane (7a) that fits over the rows (20) and over the portion of the analyzer component (1a) excluding the portion extending from the rows (20) to the inlet port (3a) and outlet port (4a). The film or layer is preferably a single-sided or double-sided tape that adheres to the surface of the analytical instrument component (1a) on one side, and to the film or layer including the inlet port (3a) and outlet port (4a) if the platform (7) does not cover both ports.

[0084] In one embodiment, the inlet port (3a) and outlet port (4a) can be configured as small openings, for example, at the bottom of the inlet tank (3) and outlet tank (4), rather than as separate layers with aligned holes. In this case, the tape adheres to the bottom of the tanks (3) and (4), but still does not adhere over the openings defining the inlet port (3a) and outlet port (4a).

[0085] In one embodiment shown in Figure 2, the platform (7) includes a shoulder (7b) which rests around the upper surface (2) of the analytical instrument component (1a) and extends sufficiently upward to provide a base for a removable cap (30—shown in Figures 5A and 5B).

[0086] In one embodiment shown in Figure 3, a single row (20) is employed, with a platform (7) including shoulders (7b) mounted on either side of the row (20), which extends sufficiently upward to provide a base for a removable cap (30). When a single row (20) is employed, it will be understood that the width of the row can extend to cover most of the top surface (2) of the analytical instrument component (1a).

[0087] In each embodiment, the platform (7) extends sufficiently upward to provide a base for the inlet port (3a), the outlet port (4a), and the removable cap (30) that covers the row (20) when the cap (30) is placed on the platform (7). In one embodiment, the inlet port (3a) and the outlet port (4a) are located at the same height above the top surface of the row (20). In other embodiments, the inlet port (3a) and the outlet port (4a) are located at different heights above the top surface of the row (20). It will be understood that the inlet tank (3) / inlet port (3a) is interchangeable with the outlet tank (4) / outlet port (4a), as the only difference is the location where the fluid (not shown) is first introduced. For simplicity, the left side of the analyzer (1) is sometimes referred to herein as the proximal side, and the right side of the analyzer (1) is referred to as the distal side. Similarly, for convenience and to relate to any assignment of proximal and distal sides, we define the proximal side as receiving fluid and the distal side as collecting fluid.

[0088] In each embodiment, a sealed fluid conduit is formed from the intake port (3a) to the outlet port (4a) through a space defined by the row (20), platform (7), and cap (30). This conduit allows the placement of the hydrophobic fluid layer to be located across the well (10) when filled with the analytical component (60). The hydrophobic fluid layer has depth, the maximum depth being defined by the height of the platform (7). It will be understood that the hydrophobic fluid added to the intake tank (3) crosses from the intake port (3a) through the conduit to the outlet port (4a). When the intake tank (3) and outlet tank (4) are employed, the addition of excess fluid to the intake tank provides equal amounts of fluid to both tanks after equilibrium is achieved. Addition of hydrophobic fluid to tank (3) can be performed with a pipette, syringe, or pump.

[0089] The hydrophobic fluid must be biocompatible, especially when used with cells as an analytical component (60), meaning that the fluid is not toxic to the cells. In addition, any biocompatible hydrophobic fluid used must be insoluble in water and have a density less than water, so that the hydrophobic fluid layer floats on water. Preferably, the hydrophobic fluid used is silicone oil, mineral oil, etc.

[0090] Figure 4 shows an enlarged sub-view of a row (20) containing wells (10). Each well (10) has a floor (12), a diameter (14), and a height (15). In one embodiment, the density of wells in the row (20) is at least about 10 wells per square millimeter. In one embodiment, each well (10) has a height (15) of about 50 to about 300 microns and a diameter (14) of about 50 to about 300 microns. In one embodiment, the shape of the wells (10) is cylindrical. The wells (10) are aligned in the row (20) such that the closest distance between the edges of adjacent wells (10a) and (10b) is at least about 10 microns. The size can be any value or partial range within the stated range, including the endpoints.

[0091] In the analytical apparatus (1), each well (10) is configured to perform the analysis of a single test compound placed on an analytical component (60), such as a bead. Such analysis is preferably performed by introducing a single bead into each well (10). Such a bead contains multiple copies of a single test compound typically synthesized on a bead by conventional split / pool combination synthesis. Other test compounds placed in the wells include, for example, mammalian cells, aqueous solutions containing buffers, salts, and cellular nutrients.

[0092] Figures 5A and 5B show the placement of the cap (30) over the platform (7), which in this case forms the outer wall or shoulder (7b). Once placed, the cap (30) creates a sealed space defined by the bottom surface (31) of the cap (30), the platform (7), and the analytical instrument component (1a). The inlet port (3a) and outlet port (4a) are both located within the sealed space, thereby defining a fluid conduit that extends throughout the entire sealed space, starting at the inlet port (3a) and ending at the outlet port (4a). This fluid conduit allows for the placement of a hydrophobic fluid layer over the well (10) as described above.

[0093] <Preparing the equipment> The analytical instrument components (1a) and other support structures described herein may contain any of many biocompatible materials, including, but not limited to, polymers such as cyclic olefin polymers (COP) commercially available from Zeon Specialty Materials, Inc. (San Jose, California, USA), cyclic olefin copolymers (COC) commercially available from many suppliers such as Polyplastics USA, Inc. ("Farmington Hills, Michigan, USA"), polyimides commercially available from many suppliers such as Putnam Plastics (Dayville, Connecticut, USA), polycarbonates commercially available from many suppliers such as Forster Corporation (Punam, Connecticut, USA), polydimethylsiloxanes commercially available from Edge Embossing (Medford, Massachusetts, USA), and polymethyl methacrylate commercially available from Parchem Fine & Specialty Chemicals (New Rochelle, New York, USA).

[0094] The wells (10) of the analytical apparatus component (1a) of the present invention can be readily prepared by a thermal embossing method, which is well known in the art and includes the step of pressing a pattern onto a polymer that has been softened by heating it to a temperature just above its glass transition temperature. A subsequent cooling step of the polymer provides the high density of the wells in the apparatus described herein. Alternatively, injection molding techniques can be used, which are well known in the art. Furthermore, it is possible to laser etch a solid block of biocompatible polymer to introduce a desired number of wells having appropriate size, volume, and shape, as well as a desired well density.

[0095] In the formation of the wells (10), each partition (16) is preferably at least about 10 microns in length from the first well (10a) to its nearest adjacent well (10b). However, even shorter distances are possible, such as at least about 5 microns from the first well (10a) to its nearest adjacent well (10b), or even at least about 1 micron. This shortest distance between wells (10) ensures the integrity of the wells so that a uniform aqueous solution (without spillage) is contained in each well (10), and that each well (10) contains one or more beads containing many copies of the same bonded test compound. In a preferred embodiment, the partition (16) is about 20 microns in length, measured from the nearest adjacent well, and more preferably between about 20 microns and less than about 50 microns in length. The size can be any value within the specified range, including the endpoints, or a partial range.

[0096] The wells (10) are created by a conventional thermal embossing method, in which a thermoplastic polymer is heated to a temperature slightly above its glass transition temperature to soften the plastic. A stamp is selected containing many circular prongs uniformly placed on the surface at the desired density. Each prong is sized to have a diameter and depth related to the size of the wells (10) described above. The distance between any two adjacent prongs is at least about 10 microns (i.e., the partitions (3) are at least about 10 microns thick). The stamp is sized so that the portion containing the prongs fits within the upper surface of the sheet. Sufficient force is applied to the stamp to ensure that the entire length of the prongs is pressed into the sheet. The required force depends on the degree of softness of the sheet and is readily apparent to those skilled in the art. Once the sheet has cooled, the prongs are removed to provide a sheet now containing the wells (10) and partitions (16).

[0097] Alternatively, with or without a platform (7) as part of an integrated structure, a partially formed apparatus (1) can be prepared by conventional injection molding using two mold halves: one (male mold half) with protrusions corresponding to the stamp protrusions and the other (female mold half) forming the base portion of the apparatus. The mold halves are aligned toward each other to form a cavity in the shape of the apparatus (1). Injection of a monomer or reactive oligomer composition into this cavity, followed by polymerization, provides the apparatus (1) now including wells (10) and partitions (16) (with or without the platform (7)).

[0098] In one embodiment, after thermal embossing or mold forming, a silicon dioxide coating may be applied to the upper surface of the apparatus (1), including the bottom surface (i.e., the floor wall of the well (10)), by conventional sputtering techniques. Preferably, the thickness of the silicon dioxide layer is about 0.5 to about 100 nanometers, and more preferably about 10 to 50 nanometers (the value can be any value or partial range within the stated range, including the endpoints). The silicon dioxide coating provides a reactive layer that bonds both the water-repellent layer and the biocompatible layer.

[0099] Regarding the structural specifications of the apparatus (1), after applying a silicon dioxide coating to the upper surface of the apparatus (1), including the bottom surface of the wells (10), each partition (16) is modified to include a biocompatible hydrophobic water-repellent layer that prevents the aqueous solution from spilling from one well to another. This water-repellent layer includes biocompatible hydrophobic water-repellent materials such as polyethylene, polypropylene, ethylene-propylene block copolymers, polytetrafluoroethylene, (trichloro)octadecylsilane (OTS), amorphous fluoropolymers (such as CYTOP®), and polydimethylsiloxane (PDMS).

[0100] The biocompatible water-repellent layer is created by conventional coating techniques. For example, one such technique involves applying a solution of a biocompatible water-repellent substance dissolved in a suitable solvent compatible with the apparatus to a disc. The disc is rotated to create a thin film of solution approximately 1 to 5 microns thick. The rotation is stopped, and the top surface of the apparatus (1) is placed on / inside the thin film. Within approximately 1 to 5 minutes, the apparatus (1) is removed from the disc and allowed to dry, forming a water-repellent layer approximately 1 to 5 microns thick. The value can be any value or a partial range within the stated range, including the endpoints.

[0101] In the alternative embodiment, the water-repellent biocompatible layer is formed by injection molding to the desired thickness. Since the addition of the water-repellent biocompatible layer is added to the depth of each well, it should be understood that the total depth of the wells mentioned above refers to the depth after the formation of the water-repellent layer.

[0102] In some embodiments, the analytical instrument component may further include a target capture (layer) element above the bottom of the well (10). This can function to prevent any movement of the analytical component (60) within the well (10). An exemplary target capture element, for illustrative purposes only, is poly-D-lysine (PDL). For example, dissolve enough PDL in an aqueous solution to achieve a concentration of about 0.1 mg / mL. PDL is commercially available from many suppliers. One supplier of PDL is ThermoFisher Scientific, 10010 Mesa Rim Road, San Diego, California, USA, as catalog number A389040. Other examples of target capture elements include fibronectin (ThermoFisher Scientific, catalog number 33016015), and vitronectin (Sigma Aldrich, catalog number 5051), among others.

[0103] A partially formed apparatus (1) without PDL target capture elements is immersed in a container containing a PDL solution. The immersion is continued for approximately one hour. The apparatus (1) is removed and allowed to dry. The hydrophobic coating on the top surface of the apparatus (1) slows down the deposition of PDL on that surface, thereby providing target capture elements on the bottom surface of the well (10) and possibly on the side walls of the well (10).

[0104] The target capture element is biocompatible with the bottom surface (12) of the well (10) and, once deposited, adheres to the target at the site of deposition to prevent target translocation, or is biocompatible with the target when the target is in solution or suspended. Preferably, the overall properties of the target capture element are hydrophobic, but hydrophobic regions are recognized. In one embodiment, the target capture element is selected to adhere to the bottom surface (12) of the well (10) and to the target deposited thereon. In each embodiment, the binding of the target to the target capture element is approximately 1 × 10⁻⁶ -3 It does not exceed and, more comfortably, 1 × 10 -5 Provides a Kd not exceeding μmol / μL (the value can be any value or a partial range within the stated range, including the endpoints). Target capture elements include substances such as poly(amino acids), DNA, RNA, siRNA, antibodies, antibody fragments, proteins, and polypeptides. Specific target capture elements are selected based on the adopted target, and the selection is well known to those skilled in the art. In one embodiment, the target is mammalian cells such as human HeLa cells, and the target capture element is a polymer of D-lysine (PDL). Approximately 1 × 10⁻⁶ 9 From approximately 1 x 10 14 A polymer of D-lysine having 1 lysine residue is preferred (the value can be any value or a partial range within the specified range, including the endpoints).

[0105] The term "target" refers to a substance, such as a biological substance, whose binding affinity to a test compound and, optionally, the biological effects of that binding, are desired. Exemplary targets include monoclonal or polyclonal antibodies, fragments of monoclonal or polyclonal antibodies, mammalian cells, DNA, RNA, siRNA, proteins (e.g., fusion proteins, enzymes, cytokines, chemokines, etc.), viruses, and the like. In a preferred embodiment, the target is a mammalian cell, such as a human cell.

[0106] When a hydrophobic biocompatible layer is used in combination with a target capture element, the apparatus (1) described herein enables the maintenance of reproducible detection of cells deposited in wells with extremely high density per square millimeter, as well as in wells (2) using electromagnetic energy detection means (e.g., light). The presence of the hydrophobic biocompatible layer described herein prevents or eliminates spillage of aqueous solutions from adjacent wells.

[0107] <Platform Integration> In one embodiment, the platform (7) includes a film or layer that fits over at least a portion of the upper surface of the analyzer components (1a) other than the row (20), the portion extending from the row (20) to the intake port (3a) and the outlet port (4a). In one embodiment, this layer or film (7a) may include a double-sided tape, such as a pressure-sensitive adhesive (PSA), configured to surround the row (20) but not to extend over it. In another embodiment, this layer or film (7a) may include a thin sheet of plastic, also configured to surround the row (20) but not to extend over it. PSA tapes are well known in the art and are available from numerous vendors, including, for example only, Adhesive Transfer Tape F9473PC from 3M Company, St. Paul, Minnesota, USA.

[0108] In one embodiment, the platform (7) is pre-fabricated to include notches for each of the rows (20) and includes a membrane (7a) extending from the proximal end of the row (20) to the inlet port (3a) and from the distal end of the row (20) to the outlet port (4a). This sheet is preferably prepared by conventional methods well known in the art. In one embodiment, the platform (7) includes shoulders (7b) extending upward from the top surface (2) of the cap (30) or downward from its bottom surface (31). These shoulders (7b) are positioned to isolate the rows (20).

[0109] Generally, the platform, whether as a membrane (7a) or shoulder (7b), has a thickness (height) of about 50 to about 1,000 microns, and preferably about 100 to about 500 microns (the value can be any value or a partial range within the stated range, including the endpoints).

[0110] Next, upon adoption, the fluid inlet (3) and fluid outlet (4) are fixed to the device component (1b). In one embodiment, the fluid inlet (3) includes an inlet tank, and the fluid outlet (4) includes an outlet tank. Both tanks have wells that partially extend downward from the top of the tank but do not lead to the bottom of the tank. A hole is drilled in the base of the tank, extending through the tank and exiting the tank, where it encounters a receding column (20). The bottom end of the hole in the inlet tank is designated as the inlet port (3a), and the bottom end of the hole in the outlet tank is designated as the outlet port (4a). This hole functions to measure the amount of fluid passing into the sealed fluid passage (5).

[0111] Alternatively, the wells within each tank extend downward from the top of the tank and down to the bottom of the tank. At the base of each well is a sheet or membrane containing a hole aligned with the bottom of each tank. Each of the holes defines either an inlet port (3a) or an outlet port (4a) and is used to measure the amount of fluid passing through the passage (5).

[0112] The fluid inlet (3) and fluid outlet (4) are manufactured by conventional techniques such as injection molding. Similarly, the plastic sheets used to form the inlet port (3a) and outlet port (4a) are well known in the art and are made to be inert to the hydrophobic fluid used.

[0113] The placement of these components onto the apparatus components (1b) is also carried out by conventional techniques well known in this industry. For example, double-sided tape such as PSA is used to bond each inlet (3) and outlet (4) to the platform (7). Alternatively, UV-inducible adhesives or conventional chemical bonding can be used.

[0114] Once these components are in place, the apparatus is complete and ready to receive the cap (30). However, prior to placing the cap (30), analytical components are added to the well by conventional methods. One or more analytical components can be added prior to or after placing the inlet (3) and outlet (4) onto the apparatus component (1b).

[0115] <Cap> The cap (30) includes a biocompatible and removable membrane or sheet that reversibly adheres to the platform (7). The membrane or sheet is preferably gas-permeable and configured to conform to the contour of the platform to which it is attached. Examples of suitable membranes or sheets include Mylar plate sealers for microtiter plates from Thermo Fisher Scientific (see above). In one embodiment, the top surface of the cap (30) has accessories such as a handle, tab, threads, or any other element that facilitates removal of the cap from the analyzer (1).

[0116] <Method> In practice, first, the well (10) is partially or completely filled with the analytical component and aqueous solution corresponding to the requirements of the analysis to be performed (e.g., pH, buffer, salt, etc.).

[0117] The cap (30), after filling, is fitted onto the platform (7), thereby forming a sealed conduit or passage (7) extending over each row (20) containing the wells (10). To protect the contents of each well (10) from contamination and / or evaporation, a biocompatible hydrophobic fluid layer is introduced into the intake port (3) in sufficient quantity for the hydrophobic fluid layer to flow downward into the intake tank and out through the intake port (3a). The hydrophobic fluid layer flows over the surface (2) of the row (20), filling any partially filled wells (10) with the hydrophobic fluid, and this fluid also accumulates in the passage (5) up to the bottom surface (31) of the cap (30). Excess hydrophobic fluid layer crosses through the outlet port (4a). The fluid is introduced from a suitable tank such as a pipette or syringe, or via a pump. The fluid injection rate is selected to ensure that the analytical components (60) in the well (10) flow horizontally across the surface of the column (20) without interruption. Preferably, the fluid is injected at a rate not exceeding approximately 100 μL per second.

[0118] In this regard, the cap (30) can be retained or removed, and the analysis may be allowed to continue until completion.

[0119] Upon completion of the analysis, remove the cap (if retained) and quantify the analytical results. Identify the wells (10) exhibiting biological activity and determine the compounds bound to the beads.

Claims

1. Analytical device (1), i) An analytical instrument component (1a) having at least one row (20) of wells (10) defined by a well bed (12), a well diameter (14), and a well height (15), wherein each first well (10a) is separated from an adjacent second well (10b) by a partition (16), The analytical apparatus component (1a) terminates on the upper surface (2) including the surface partition (16) and the top of the well (10), ii) To retract the rows (20) from the upper surface of the platform (7), the platform (7) extends over at least a portion of the surface (2) of the analytical instrument component (1a), but does not extend over the rows (20), iii) Each row (20) is comprised of one end which terminates at an inlet port (3a) and the other end which terminates at an outlet port (4a), The analytical instrument component (1a) and platform (7) are configured to receive and maintain the biocompatible removable cap (30). The cap (30) has a bottom surface (31), The configuration of the analyzer component (1a), platform (7), inlet (3a), outlet (4a), and bottom surface (31) of the cap (30) ensures that the cap (30) is maintained on the platform (7), isolating the row (20), thereby defining a sealed fluid passage (5) extending from the inlet port (3a) to the outlet port (4a) through a space defined by the upper surface (2) of the analyzer component (1a), the platform (7), and the bottom surface (31) of the cap (30), the height of which is defined by the height of the platform (7). The sealed passage (5) provides the fluid communication substantially horizontal to the top of the well (10). Analyzer (1).

2. The row (20) has a density of at least 10 wells per square millimeter. The apparatus according to claim 1.

3. Each of the partitions (16) of the apparatus (1) includes a hydrophobic water-repellent layer incorporated on at least a portion of the surface (2) on the partition (16), The apparatus according to claim 2.

4. The apparatus includes a single row and a single pair of intake tanks (3) / intake ports (3a) and outlet tanks (4) / outlet ports (4a), The apparatus according to claim 1.

5. The apparatus includes a plurality of rows (20) and a plurality of pairs of intake tanks (3) / intake ports (3a) and outlet tanks (4) / outlet ports (4a), Each pair is arranged in its respective column (20). The apparatus according to claim 1.

6. The platform (7) is incorporated on a portion of the top surface of the analytical instrument component (1a), and extends sufficiently upward so that the top of the platform (7) is higher than the intake port (3a) and the outlet port (4a). The apparatus according to claim 1.

7. The intake port (3a) is in fluid communication with the intake tank (3b), and the outlet port (4a) is in fluid communication with the outlet tank (4b). The apparatus according to claim 1.

8. The platform (7) is incorporated on the bottom surface of the cap (30), and extends sufficiently downward so that the bottom surface (31) of the cap (30) does not fall lower than the inlet port (3a) and outlet port (4a). The apparatus according to claim 1.

9. The platform (7) is a membrane (7a) placed on a portion of the surface (2) other than the rows (20), which causes the rows (20) to recede beneath the platform membrane (7a), thereby isolating the rows (20). The apparatus according to claim 1.

10. The platform (7) is positioned adjacent to each side of the row (20) and is a pair of shoulders (7b) extending from the intake port (3a) to the outlet port (4a), retracting the row (20) below the shoulders (7b). The apparatus according to claim 1.

11. The platform (7) is a series of shoulders (7b) arranged around the surface (2), with the row (20) set back below the shoulders (7b). The apparatus according to claim 1.

12. The apparatus (1) includes 10,000 to 2,500,000 wells (10), The apparatus according to claim 1.

13. The intake tank (3) is a syringe or pipette containing the desired fluid, and the tip of the outlet of the syringe or pipette fits into the intake port (3a), and when fitted, it enables the introduction of the fluid into the passage (5). The apparatus according to claim 7.

14. The intake tank (3) is a needle connected to a pump containing the desired fluid, and the needle engages with the intake port (3a) so that the pump can continuously deliver the fluid to the passage (5) under controlled pressure and delivery rate. The apparatus according to claim 7.

15. The intake tank (3) is a well fixed in a predetermined position above the intake port (3a), and the well is in fluid communication with the intake port (3a) such that the fluid in the intake tank (3) flows through the intake port (3a), then flows into the passage (5), and passes through the passage (5). The apparatus according to claim 7.

16. The fluid outlet (4) overflows from the outlet port (4a), and any fluid exceeding the volume capacity of the passage (5) flows out from the outlet port (4a). The apparatus according to claim 1.

17. The fluid outlet (4a) is a well fixed at a predetermined position on the outlet port (4a), and the well is in fluid communication with the outlet port (4a), and when the volume capacity of the passage (3) is exceeded, the fluid flows from the outlet port (4a) into the fluid outlet (4), and then flows into the outlet (4). The apparatus according to claim 7.

18. The well (10) of the apparatus contains sufficient analytical components (60) for performing the analysis. The apparatus according to claim 1.

19. The well is covered with a hydrophobic fluid layer. The apparatus according to claim 1.

20. It is a kit of parts, A) Analytical device (1), i) An analytical instrument component (1a) having at least one row (20) of wells (10) defined by a well bed (12), a well diameter (14), and a well height (15), wherein each first well (10a) is separated from an adjacent second well (10b) by a partition (16), An analytical apparatus component (1a) terminates at the upper surface (2) which includes the surface of the partition (16) and the top of the well (10), ii) To retract the rows (20) from the top surface of the platform (7), the platform (7) extends over at least a portion of the surface (2) of the analytical instrument component (1a), but does not extend over the rows (20), iii) Each row (20) terminates at one end with an inlet port (3a) and the opposite end with an outlet port (4a), Equipped with, The analyzer component (1a) and platform (7) are configured to receive and maintain a removable biocompatible cap (30). Analytical device (1), B) A removable biocompatible cap (30) having a bottom surface (31), The configuration of the analyzer component (1a), platform (7), inlet (3a), outlet (4a), and bottom surface (31) of the cap (30) ensures that the cap (30) is maintained on the platform (7), isolating the row (20), thereby defining a sealed fluid passage (5) extending from the inlet port (3a) to the outlet port (4a) through a space defined by the upper surface (2) of the analyzer component (1a), the platform (7), and the bottom surface (31) of the cap (30), the height of which is defined by the height of the platform membrane (7a). The passage (5) provides the fluid communication substantially horizontal to the top of the well (10). A removable biocompatible cap (30) and Equipped with, A kit of parts.

21. Analytical device (1), A) i) An analytical instrument component (1a) having at least one row (20) of wells (10) defined by a well bed (12), a well diameter (14), and a well height (15), wherein each first well (10a) is separated from an adjacent second well (10b) by a partition (16), An analytical apparatus component (1a) terminates on the upper surface (2) which includes the surface of the partition (16) and the top of the well (10), ii) To retract the rows (20) from the top surface of the platform (7), the platform (7) extends over at least a portion of the surface (2) of the analytical instrument component (1a), but does not extend over the rows (20), iii) Each row (20) terminates at one end with an inlet port (3a) and the opposite end with an outlet port (4a), Equipped with, The device component (1b) is configured to receive and retain the biocompatible removable cap (30), B) A removable biocompatible cap (30) having a bottom surface (31), The configuration of the analyzer component (1a), platform (7), inlet (3a), outlet (4a), and bottom surface (31) of the cap (30) ensures that the cap (30) is supported on the platform (7), isolating the row (2), thereby defining a sealed fluid passage (5) extending from the inlet port (3a) to the outlet port (4a) through a sealed space defined by the top surface (2) of the analyzer component (1a), the platform (7), and the bottom surface (31) of the cap (30), the height of which is defined by the height of the platform (7). The sealed fluid passage (5) provides the fluid communication substantially horizontal to the top of the well (10), The sealed fluid passage contains a hydrophobic fluid, Cap (30), Equipped with, Analyzer (1).

22. It is an analytical device, a) an analytical instrument component having a top surface and b) a biocompatible removable cap having a bottom surface that fits therein, wherein the top surface of the analytical instrument component includes at least one row having a plurality of wells, each of the plurality of wells being defined by a well bed, a well diameter, and a well height, and the top surface of the analytical instrument component includes the top surfaces of the plurality of wells, the analytical instrument component and the biocompatible removable cap, A platform having a top surface, extending over each side of the at least one row and terminating at the proximal and distal ends of the analytical instrument components, but not extending over the at least one row, thereby receding each of the at least one row from the top surface of the platform, thereby defining a recess located beneath the top of the platform, the bottom of which includes the top surface of the analytical instrument components, and the platform, Equipped with, The biocompatible removable cap fits onto the platform of the analytical instrument component, thereby isolating the recess, which terminates at one end at the intake tank / intake port and at the other end at the outlet tank / outtake port. The recess, together with the platform and the bottom surface of the biocompatible removable cap, defines a sealed passage or conduit from the intake tank / intake port to the outlet tank / outlet port. The sealed passage or conduit provides a substantially horizontal fluid communication with respect to the top of the well. Analyzer.

23. The apparatus according to claim 22, comprising a single row and a single pair of the intake tank / intake port and the outlet tank / outtake port, wherein the intake tank is in fluid communication with the intake port and the outlet tank is in fluid communication with the outlet port.

24. The apparatus includes a plurality of rows and a plurality of pairs of intake tanks / intake ports and outlet tanks / outlet ports, each pair being aligned with each row, each intake port being in fluid communication with an intake tank, and each outlet port being in fluid communication with an outlet tank. The apparatus according to claim 22.

25. The platform is incorporated on a portion of the upper surface of the analytical instrument component, and extends sufficiently upward so that the upper surface of the platform is higher than the intake port and the outlet port. The apparatus according to claim 22.

26. The intake port is in fluid communication with the intake tank, and the outlet port is in fluid communication with the outlet tank. The apparatus according to claim 22.

27. The platform is incorporated on the bottom surface of the biocompatible removable cap and extends sufficiently downward so that the bottom surface of the biocompatible removable cap does not become lower than the inlet and outlet ports. The apparatus according to claim 22.

28. The platform is a membrane positioned over a portion of the surface other than the at least one row, which causes the at least one row to recede beneath the platform membrane, thereby isolating the at least one row. The apparatus according to claim 22.

29. The platform is a pair of shoulders positioned adjacent to each side of the at least one row and extending from an inlet port to an outlet port, receding the at least one row below the shoulders. The apparatus according to claim 22.

30. The platform is a series of shoulders arranged around the upper surface of the analyzer, with at least one row receding below the shoulders. The apparatus according to claim 22.

31. The apparatus includes 10,000 to 2,500,000 wells. The apparatus according to claim 22.

32. A fluid outlet is provided for overflow from the outlet port, and any fluid exceeding the volumetric capacity of the sealed passage or conduit flows out from the outlet port. The apparatus according to claim 22.

33. The fluid outlet is a well fixed at a predetermined position on the outlet port, the well is in fluid communication with the outlet port, and fluid exceeding the volume capacity of the sealed passage or conduit flows out from the fluid outlet port into the fluid outlet. The apparatus according to claim 32.

34. It is an analytical device, a) an analytical instrument component having a top surface and b) a biocompatible removable cap having a bottom surface that fits therein, wherein the top surface of the analytical instrument component includes at least one row having a plurality of wells, each of the plurality of wells being defined by a well bed, a well diameter, and a well height, and the top surface of the analytical instrument component includes the top surfaces of the plurality of wells, the analytical instrument component and the biocompatible removable cap, A platform having a top surface, extending over each side of the at least one row and terminating at the proximal and distal ends of the analytical instrument components, but not extending over the at least one row, thereby receding each of the at least one row from the top surface of the platform, thereby defining a recess located beneath the top of the platform, the bottom of which includes the top surface of the analytical instrument components, and the platform, Equipped with, The configuration of the analytical instrument components, the platform, the intake tank / intake port, the outlet tank / outtake port, and the bottom surface of the removable biocompatible cap allows the removable biocompatible cap to be fitted onto the platform, isolating the recess, which is terminated at one end at the intake tank / intake port and at the other end at the outlet tank / outtake port. The recess, together with the platform and the bottom surface of the biocompatible removable cap, defines a sealed passage or conduit from the intake tank / intake port to the outlet tank / outlet port. The removable biocompatible cap can be placed on or removed from the analytical instrument component. The sealed passage or conduit provides a substantially horizontal fluid communication with respect to the top of the well. Analyzer.

Images