Modular well plate system with reusable frame

Abstract

Described herein is a modular well plate system having a reusable frame configured to accept multiple disposable modules, which is useful, among other things, for conducting multiplexed analytical scientific studies.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Patent Application No. 63 / 371,762, filed August 18, 2022, the contents of which are incorporated herein by reference in their entirety. [Background technology]

[0002] Specialized culture plates for analyzing microbial (e.g., microbiome) samples can be expensive to purchase as whole units or plates. Additionally, the reagents and samples used to prepare these plate samples can be costly and time-consuming to prepare in large quantities.

[0003] It is desirable to have a system that allows researchers to evaluate the system and methodology on small batches or volumes to hone their skills before moving on to more costly and time-consuming studies that utilize a full-size plate (or multiple plates). Summary of the Invention

[0004] In one embodiment, a modular well plate system is described that includes a reusable frame configured to temporarily secure a plurality of disposable modular wells (modules).

[0005] In another aspect, a modular well plate system is described that includes a plurality of disposable modules, each having a plurality of chambers and one or more alignment features, and a reusable frame that includes horizontal and vertical reference surfaces, a plurality of receptacles for the modules, and one or more corresponding alignment features.

[0006] These and other aspects, which will become apparent in the detailed description that follows, were achieved through the inventors' discovery of a novel modular well plate system. [Brief explanation of the drawings]

[0007] [Figure 1A] FIG. 1 is an isometric view of the modular well-plate system showing the reusable frame with all eight co-culture modules mounted on it. [Figure 1B] Isometric view of the modular well-plate system showing the reusable frame with all 18 co-culture modules mounted on it. [Figure 2A] FIG. 1 is a plan view of a modular well plate system with a reusable frame. [Figure 2B] FIG. 1 is a plan view of a modular well plate system with a reusable frame. [Figure 3A] Isometric view of an individual module, where multiple modules are combined with a frame to form a well plate system. Two well volumes are connected together to form an individual co-culture module. [Figure 3B] Isometric view of an individual module, where multiple modules are combined with a frame to form a well plate system. Two well volumes are connected together to form an individual co-culture module. [Figure 4A] 1 is a top view of individual modules, each showing a measurement window or opening. [Figure 4B] 1 is a top view of individual modules, each showing a measurement window or opening. [Figure 5A] FIG. 10 is an isometric view of the bottom of an individual module showing the registration and alignment features on the bottom surface, as well as the alignment features. [Figure 5B] FIG. 10 is an isometric view of the bottom of an individual module showing the registration and alignment features on the bottom surface, as well as the alignment features. [Figure 6A]1 is an isometric view of a modular well plate system with a reusable frame, shown in use when several individual modules are removed from the frame and partially installed. [Figure 6B] 1 is an isometric view of a modular well plate system with a reusable frame, shown in use when several individual modules are removed from the frame and partially installed. [Figure 7A] FIG. 1 is an isometric view of a reusable frame. [Figure 7B] FIG. 1 is an isometric view of a reusable frame. [Figure 8A] FIG. 10 is a top view of the reusable frame showing the flexure tabs used to align and register the individual modules. [Figure 8B] FIG. 10 is a top view of the reusable frame showing the flexure tabs used to align and register the individual modules. [Figure 9] 1 shows a reusable frame with a logo plague. DETAILED DESCRIPTION OF THE INVENTION

[0008] Illustrative embodiments of the present invention are described herein. While the following detailed description includes many specific details for purposes of illustration, those skilled in the art will appreciate that variations and modifications of the following details are within the scope of the present invention. Accordingly, the following embodiments of the present invention are set forth without any loss of generality to, and without imposing limitations on, the claimed invention.

[0009] One embodiment of the present disclosure relates to an apparatus comprising a reusable frame configured to temporarily hold a plurality of individual disposable microplate modules. In some embodiments, these individual disposable modules comprise dedicated wells, co-culture pairs, or other combinations thereof. In some embodiments, the modules are designed to fit snugly into the reusable frame to form an assembly suitable for attachment to various microplate readers for scientific interrogation of samples contained within the modules.

[0010] The names of the components shown in Figures 1A to 9 are as follows. [Table 1]

[0011] 1A and 1B, a modular well plate system 100 is shown that includes a reusable frame 300 and a plurality of disposable modular wells 200 (also called modules). Figure 1A shows eight modules, and Figure 1B shows eighteen modules.

[0012] 2A and 2B, a top view of the modular well plate system is shown in which the position of the reusable frame 300 is aligned via reference planes 104 (horizontal) and 110 (vertical) with respect to a measurement device used to measure parameters of samples contained within the modular well plate system 100. The frame is shown with an origin indicator 102 designed to identify the origin of the reusable frame 300 and a coordinate system 106 configured to identify the plurality of disposable modular wells 200. A horizontal alignment mechanism 108 and a vertical alignment mechanism 112 are configured to temporarily secure the modular wells 200 relative to the frame 300.

[0013] 3A-5B, a disposable modular well 200 (module) is shown having a top surface 202, two chambers (shown but not numbered), a horizontal alignment surface 204 configured to align the module with a corresponding feature 108 on the reusable frame 300, and a vertical alignment surface 206 configured to align the module with a corresponding feature 112 on the reusable frame 300. The module is also shown to have a measurement window or opening 208, a bottom alignment surface 210, and an alignment feature 212.

[0014] 6A-8A, a reusable frame 300 is illustrated. The frame is shown with a plurality of measurement windows or openings 302, a plurality of module support ledges 304, a plurality of alignment flexures 306, a perimeter ridge 308, an origin cross section 310, a logo plate 312, a central support rib 314, a spill cache 316, an internal ridge 318, a module introduction mechanism 320, rounded frame corners 322, and a secondary alignment flexure 324.

[0015] Referring to FIG. 9, an alternative location for the logo plate 312 is illustrated.

[0016] The perimeter and alignment features described herein are designed according to ANSI standards for common microplate sizes (e.g., 127.76 mm x 85.48 mm), and the modular well plate system 100, assembled with an optional lid (not shown), is designed to fit into equipment and devices common in laboratory and diagnostic practices for microplates and similar products.

[0017] Another aspect is a novel modular well plate system 100, comprising: A reusable frame 300; B one or more modular wells 200; The reusable frame 300 is configured to receive and temporarily secure a plurality of modular wells 200, which may be disposable or alternatively reusable.

[0018] The reusable frame 300, sometimes referred to as an alignment frame, is configured to securely but temporarily secure and align one or more individual modules 200 to the frame. Once the modules 200 are temporarily secured to the reusable frame 300, the modular well plate system 100 can be placed into an apparatus or device common to laboratory and diagnostic practices for microplates and similar products (e.g., Molecular Devices' SpectraMax, Tecan Infinite, or Cerillo's Stratus).

[0019] Another aspect is a novel modular well plate system 100, comprising: a) a plurality of disposable modules 200, each comprising: i) at least one chamber, and ii) a plurality of modules each comprising one or more alignment features (204, 206); b) a reusable frame, i) at least one horizontal reference plane 104; ii) at least one vertical reference plane 110; iii) a plurality of receivers surrounded by the reference surface, each receiver configured to receive one of the plurality of modules; iv) a reusable frame having one or more alignment features (108, 112) corresponding to one or more alignment features in the module; The modules are individually configured for experimental purposes, the modules are temporarily secured to the frame via respective alignment features on each module; The invention relates to a well plate system in which a frame is configured to mate with a standard multi-well plate reader and present temporarily fixed modules for measurement.

[0020] Another aspect is a novel modular well plate system 100, in which a reusable frame 300: a) at least one feature defining a horizontal reference plane 104; b) at least one feature defining a vertical reference plane 110, wherein the horizontal reference plane 104 and the vertical reference plane 110 function together to align the reusable frame 300 from the present module well(s) 200 or in the device making the measurement; c) a plurality of receptacles surrounded by a reference surface, each receptacle configured to receive an individual module 200, each optionally further comprising: a window or opening 302 to allow the device to measure samples contained within the individual modules; d) at least one vertically oriented alignment feature 112 for aligning each individual module 200 with respect to the vertical reference plane 110; and e) A modular well plate system including at least one horizontally oriented alignment mechanism 108 for aligning each individual module 200 with respect to the horizontal reference surface 104.

[0021] In another aspect, a reference plane refers to a datum plane (e.g., a wall) used as a reference position for aligning the modular well plate system (specifically the plate portion) with a desired device (or machine or apparatus, used interchangeably herein).

[0022] In another aspect, examples of the plurality of receptacles include pockets, recesses, and grooves, or other features (not numbered).

[0023] Another aspect relates to a novel modular well plate system 100, wherein the reusable frame 300 optionally comprises one or more of the following: f) at least one alignment flexure 306 configured to align an individual module with a vertically oriented alignment feature 112; g) at least one secondary alignment flexure 324 configured to align the individual modules with the horizontally oriented alignment mechanism 108; h) one or more module support ledges 304 configured to align and optionally secure individual modules 200 to the bottom surface of the frame; i) internal ridge 318; j) peripheral ridges 308 configured to cooperate with the internal ridges 318 to contain spillage and which may be used individually or in combination to support a lid or covering mechanism (not shown); k) a centrally located support rib 314 or a plurality of support ribs in a branched configuration configured to provide mechanical support while manipulating the frame and securing the modules; l) a recessed area 316 for receiving overflow sample or serving as a base for mechanical attachment in a lid or covering mechanism; m) introduction mechanism 320; n) Origin display 102, o) a coordinate system 106 for identifying individual modules; p) a designated area for placing a company logo or a fill-in plate 312 for writing or printing experimental information; and q) Rounded corners 322 that allow the frame to fit (or fit more easily) into various multi-well plate readers or similar devices.

[0024] In another embodiment, the introduction mechanism 320 includes a tapered end to aid in module placement and alignment.

[0025] In another embodiment, the origin indicator 102 can be used to indicate the proper direction of measurement and analysis.

[0026] In another aspect, alignment flexures 306 and secondary alignment flexures 324 apply a directional force to align the module with the corresponding alignment features 112 and 108, respectively. Examples of flexures that create such a force include spring tabs, precisely dimensioned features designed to create a press fit, and elastomeric components.

[0027] Another embodiment is a novel modular well plate system 100, wherein one or more modular wells 200 are: a) a plurality of chambers (e.g., 2, 3, 4, or more), each configured to contain a quantity (e.g., a liquid, a reactant, a cell, etc.), and the plurality of chambers secured or connected together (e.g., using manufacturing methods common in the art); b) at least one horizontally oriented alignment feature 204 configured to align the module with a corresponding feature 108 on the reusable frame 300; c) at least one vertically oriented alignment feature 206 configured to align the module with a corresponding feature 112 on the reusable frame 300.

[0028] In another aspect, examples of methods used to secure or connect the chambers include the use of self-tapping screws, rivets, adhesives, laser welding, heat stamping, and ultrasonic welding.

[0029] Another embodiment relates to a disposable module 200 comprising a first chamber, a second chamber, and optionally a third or subsequent chambers. Each chamber is configured to contain a volume (e.g., a first volume and a second volume). In some embodiments, the volumes are fluidly or pairwise connected so that they can be used to measure contact-independent interactions. For example, in Figures 3A and 3B, two chambers are illustrated (unnumbered). In one example, these two chambers comprise first and second volumes that can be used to measure interactions between different sets of microorganisms separated by a semipermeable membrane (not shown).

[0030] Another aspect relates to a novel modular well plate system 100, wherein one or more modular wells 200 optionally and independently comprise one or more of the following: d) a top surface 202 onto which a lid or other type of sample cover can optionally be attached and fitted; e) at least one window or opening 208 that allows for measurement of a sample contained within the chamber; f) a bottom surface 210 configured to allow the module 200 to be vertically positioned and held by a support ledge 304; and g) At least one alignment mechanism 212 used in the assembly and automation processes used to assemble the module 202.

[0031] In another embodiment, an example of alignment feature 212 includes holes for dowel pins to allow multiple components to be aligned with one another during assembly.

[0032] 1A-9, the modular well plate system 100, specifically the reusable frame 300, is optionally configured to accommodate a variety of module types (not shown), provided that the outer module dimensions fit within the recesses and alignment features of the reusable frame 300.

[0033] Another embodiment relates to a reusable frame 300 with recesses for multiple types and sizes of disposable modules (not shown). For example, a single frame may contain a mixture of different sized recesses or grooves to accommodate various combinations of module types (sizes) to enable tandem experiments.

[0034] 6A and 6B, one advantage of the modular well plate system of the present invention is that researchers do not need to populate the reusable frame 300 with modules to begin an experiment. Only one module is needed, at least to begin an experiment. Additional modules (even different types of modules) can be added during an experiment, or none at all. This is particularly useful in reducing plastic and material waste, and also in limiting the amount of expensive reagents and / or other chemicals used during experimental discovery and enhancement.

[0035] 1A and 1B, a researcher can run different types of assay and sample modules all housed in the same modular well plate system 100. Furthermore, if an experiment using a given module (or modules) does not produce the desired results, the researcher can replace that module (or modules) with a module of a different type or configuration.

[0036] Another aspect relates to a modular well plate system in which modular chambers match the volumes and spacing of standard plate sizes. Example numbers of modular chambers include 6, 12, 24, 48, 96, and 384.

[0037] In another aspect, the number of chambers present in the modular well plate system ranges from 2 to 48 (or more). Examples include 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, and 48.

[0038] Another aspect relates to a reusable frame that is configured to allow its sterilization after use, either by autoclaving, ethylene oxide gas treatment, or other processes standard in laboratory practice. Because this frame and modular well plate system may be used in sensitive environments or biologically hazardous areas, this type of design consideration is believed to aid in the reuse of frame components.

[0039] Another aspect relates to the opacity of some or all of the walls of the disposable module 200. Fluorescence measurements typically use containers with opaque walls (or, for example, walls with windows) to facilitate optical reading of the sample's response as it begins to glow. For example, a module can be designed for fluorescence, with portions optically isolating a sample volume, allowing the sample's optical emission to be isolated and measured. As an example, a fluorescent module can be paired with a non-fluorescent sample to measure contact-independent interactions or protein expression using various types of imaging modalities in one frame assembly. This can help reduce variables such as timing and environmental control during the experimental process.

[0040] Another aspect relates to an at least partially opaque module for facilitating measurement of fluorescence of a sample.

[0041] Another embodiment relates to modules that are pairs of wells designed to induce contact-independent interactions between two microbial cultures.

[0042] Another aspect relates to modules with single well chambers with round or flat bottoms, for example, of unusual sizes or geometries useful for more abstract or novel science.

[0043] Another aspect relates to modules that include a selective growth substrate, for example, the module is pretreated with the selective growth substrate.

[0044] Another aspect relates to modules that are artificial samples of standards for calibration or comparison purposes.

[0045] Another aspect relates to modules that contain specific optical density intended features or other parametric comparators used to calibrate devices or compare readings between different devices.

[0046] Another aspect relates to modules that are tissue culture treated wells designed to promote the growth of adherent cells.

[0047] Another aspect relates to modules that have been pretreated by a plasma etching process or similar process to promote cell or microbial growth in and / or along the surface of the module, sometimes referred to as tissue culture treatment.

[0048] Another aspect relates to modules that are engineered with or contain regions or mechanisms for specifically containing or isolating regions of extracellular matrix for the purpose of promoting differentiation and / or growth of different types of eukaryotic cells.

[0049] Another aspect relates to a modular well plate system in which the module(s) and frame are constructed from materials that are resistant to temperature extremes and fluctuations, which may be particularly useful for the evaluation of microorganisms classified as extremophiles.

[0050] Another aspect relates to a modular well plate system in which a reusable frame is configured to house nested versions of modules that are designed to interlock or connect with one another, for example, a larger module acts as a trough into which other modules nest to house common metabolites to be measured, constrained both by the geometry of the larger module and the reusable frame.

[0051] Another aspect relates to modules that include independent light sources that are used to take measurements or promote photosynthetic growth.

[0052] Another aspect relates to modules with individual elements and control components designed to actively manage the temperature of each module, allowing researchers to test the optimal growth temperature for a particular culture.

[0053] All references cited herein are individually incorporated by reference in their entirety. Numerous modifications and variations of the present invention are possible in light of the above teachings. Therefore, it is to be understood that, within the scope of the appended claims, the invention may be practiced otherwise than as specifically described.

Claims

1. 1. A modular well plate system comprising: a) a plurality of disposable modules, each of which i) at least one chamber, and ii) the plurality of modules comprising one or more alignment features; b) a reusable frame, i) at least one horizontal reference plane; ii) at least one vertical reference plane; iii) a plurality of receiving portions bounded by the reference surface, each receiving portion configured to receive one of the plurality of modules; iv) the reusable frame including one or more alignment features corresponding to one or more alignment features on the module; the modules are individually configured for experimental purposes; the modules are temporarily secured to the frame via respective alignment features on each module; The well plate system, wherein the frame is configured to mate with a standard multi-well plate reader and present the temporarily secured modules for measurement.

2. 2. The well plate system of claim 1, wherein the horizontal outer dimensions of the frame match the outer dimensions of a standard multi-well plate.

3. 10. The well plate system of claim 1, wherein the modules are presented in horizontal positions corresponding to the horizontal positions of one or more wells of a standard multi-well plate.

4. The well plate system of claim 3, wherein the standard multi-well plate is a 96-well plate.

5. The well plate system of claim 1 , wherein the frame is sterilizable.

6. 10. The well plate system of claim 1, wherein at least one module is a pair of wells designed to induce contact-independent interactions between two microbial cultures.

7. 10. The well plate system of claim 1, wherein at least one module is at least partially opaque to facilitate measurement of sample fluorescence.

8. 10. The well plate system of claim 1, wherein at least one module is a single flat-bottom sample well.

9. 10. The well plate system of claim 1, wherein at least one module is a single round-bottom sample well.

10. 10. The well plate system of claim 1, wherein at least one module is pretreated with a selective growth substrate.

11. 10. The well plate system of claim 1, wherein at least one module is an artificial sample of a standard value for calibration or comparison purposes.

12. 10. The well plate system of claim 1, wherein at least one module is a tissue culture treated well designed to promote the growth of adherent cells.

13. 10. The well plate system of claim 1, wherein at least one module is treated with an extracellular matrix to promote the growth of eukaryotic cells.

14. 10. The well plate system of claim 1, wherein at least one module is constructed from a material that is resistant to the effects of extreme temperatures.

15. 10. The well plate system of claim 1, wherein at least one module is configured to nest a secondary module therein.

16. 10. The well plate system of claim 1, wherein at least one module further comprises a light source for performing measurements.

17. 10. The well plate system of claim 1, wherein at least one module further comprises a light source for promoting photosynthetic growth.

18. 10. The well plate system of claim 1, wherein at least one module further comprises an element designed to actively control the internal temperature of that module.

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