Modular orifice plate system with reusable frame

Abstract

A modular orifice plate system having a reusable frame configured to receive a plurality of disposable modules is described herein. The system is particularly useful for performing multiplexing analytical science studies.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority under 35 U.S.C. § 119(e) to U.S. Provisional Patent Application No. 63 / 371,762, filed on August 18, 2022. The contents of said application are incorporated herein by reference in their entirety. Background Art

[0003] Specialized culture plates for analytical analysis of microbial (e.g., microbiome) samples can be expensive to purchase in whole units or plates. In addition, the reagents and samples used in preparing these plate samples can be costly or time-consuming to prepare in larger quantities.

[0004] It would be desirable to have a system where researchers could evaluate their systems and methods in small batches or quantities to hone their techniques before undertaking more costly or time consuming studies utilizing a full-size plate (or plates). Summary of the invention

[0005] In one aspect, a modular well plate system is described that includes a reusable frame configured to temporarily adhere a plurality of disposable modular wells (modules).

[0006] In another aspect, a modular well plate system is described, comprising: a plurality of disposable modules, each module having a plurality of chambers and one or more alignment features; and a reusable frame comprising a horizontal reference plane and a vertical reference plane, a plurality of receiving areas for the modules, and one or more corresponding alignment features.

[0007] These and other aspects that will become apparent in the following detailed description have been achieved by a novel modular orifice plate system discovered by the inventors. BRIEF DESCRIPTION OF THE DRAWINGS

[0008] Figure 1A and Figure 1B is an isometric view of a modular well plate system depicting a reusable frame fully populated with 8 or 18 co-culture modules, respectively.

[0009] Figure 2A and Figure 2B is a top view of a modular well plate system with reusable frames.

[0010] Figure 3A and Figure 3B is an isometric view of a single module, which is combined with the frame to form a perforated plate system. Figure 3A and Figure 3BIn the experiment, two microwell volumes were connected together to form a single co-culture module.

[0011] Figure 4A and Figure 4B is a top view of the individual modules, each showing the measurement window or opening.

[0012] Figure 5A and Figure 5B is an isometric view depicting the bottom of an individual module showing the bottom alignment and registration features and the alignment features.

[0013] Fig. 6A and Figure 6B is an isometric view of a modular well plate system with a reusable frame. Fig. 6A and Figure 6B In , several individual modules have been removed from the frame to illustrate their use when partially populated.

[0014] Fig. 7A and Figure 7B is an isometric view of a reusable framework.

[0015] Fig. 8A and Figure 8B is a top view of the reusable frame showing the flexure tabs used to align and register the individual modules.

[0016] Fig. 9 A reusable frame with a logo tag is shown. DETAILED DESCRIPTION

[0017] Exemplary aspects of the present invention are described herein. Although the following detailed description contains many specific details for illustrative purposes, it will be appreciated by those skilled in the art that variations and modifications of the following details are within the scope of the present invention. Therefore, the following aspects of the present invention are set forth without any loss of generality to the claimed invention and without imposing limitations thereon.

[0018] One aspect of the present invention relates to a device comprising: a reusable frame configured to temporarily hold a plurality of individual disposable microplate modules. In some aspects, the individual disposable modules include: dedicated wells, co-culture pairs, or other combinations thereof. In some aspects, the modules are designed to fit tightly into the reusable frame, thereby forming an assembly suitable for fitting in a variety of microplate readers for scientific examination of samples contained in the modules.

[0019] Figures 1A to 9 The names of the parts shown are as follows:

[0020]

[0021]

[0022] refer to Figure 1A and Figure 1B , a modular well plate system 100 is shown, which includes: a reusable frame 300 and a plurality of disposable modular wells 200 (also referred to as modules). Figure 1A Eight modules are shown. Figure 1B 18 modules are shown.

[0023] refer to Figure 2A and Figure 2B , a top view of a modular well plate system is shown, wherein the position of a reusable frame 300 is aligned with a measurement device for measuring a parameter of a sample contained within the modular well plate system 100 by reference planes 104 (horizontal) and 110 (vertical). 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 allow identification of a plurality of disposable modular wells 200. Horizontal registration features 108 and vertical registration features 112 are configured to temporarily adhere the modular wells 200 to the frame 300.

[0024] refer to FIG. 3A to FIG. 5B , a disposable modular well 200 (module) is shown. The module has a top surface 202; two chambers (shown, but not numbered); a horizontal registration surface 204 configured to align the module with a corresponding feature 108 on a reusable frame 300; and a vertical registration surface 206 configured to align the module with a corresponding feature 112 on the reusable frame 300. The module is also shown with a measurement window or opening 208, a bottom registration surface 210, and an alignment feature 212.

[0025] refer to 6A to 8A , a reusable frame 300 is shown. The frame is shown having a plurality of measurement windows or openings 302, a plurality of module support flanges 304, a plurality of registration flexures 306, a perimeter ridge 308, an origin cutout 310, a logo tab 312, a central support rib 314, a spill buffer 316, an internal ridge 318, a module introduction feature 320, a rounded frame corner 322, and a secondary registration flexure 324.

[0026] refer to Fig. 9 , showing an alternative location for the logo label 312.

[0027] The perimeter features and alignment features described herein are designed according to ANSI standards for common microplate sizing (e.g., 127.76 mm x 85.48 mm), and the modular well plate system 100 is designed to fit into instruments and devices commonly used in laboratory and diagnostic practices that utilize microplates and similar products when assembled, along with an optional cover (not shown).

[0028] Another aspect relates to a novel modular well plate system 100 comprising:

[0029] A reusable frame 300; and,

[0030] B one or more modular holes 200;

[0031] Wherein the reusable frame 300 is configured to receive and temporarily adhere a plurality of modular apertures 200, and the modular apertures 200 are disposable, or alternatively reusable.

[0032] 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 adhered to the reusable frame 300, the modular well plate system 100 can then be placed into instruments and devices commonly used in laboratory and diagnostic practices for microplates and similar products (such as modular devices SpectraMax, Tecan Infinite or Cerillo Stratus).

[0033] Another aspect relates to a novel modular well plate system 100 comprising:

[0034] a) a plurality of disposable modules 200, each module comprising:

[0035] i) at least one chamber; and

[0036] ii) one or more registration features (204, 206); and,

[0037] b) a reusable framework, the reusable framework comprising:

[0038] i) at least one horizontal reference plane 104;

[0039] ii) at least one vertical reference plane 110;

[0040] iii) a plurality of receiving areas defined by the reference plane, each receiving area being configured to receive one of the plurality of modules;

[0041] iv) one or more registration features (108, 112) corresponding to one or more registration features on the module;

[0042] in:

[0043] Modules are configured individually for experimental purposes;

[0044] The modules are temporarily adhered to the frame via respective registration features of each module; and

[0045] The frame is configured to mate with a standard multiwell plate reader and presents the modules to be temporarily attached for taking measurements.

[0046] Another aspect relates to a novel modular well plate system 100, wherein a reusable frame 300 comprises:

[0047] a) defining at least one feature of a horizontal reference plane 104;

[0048] b) defining at least one feature of a vertical reference plane 110, wherein the horizontal reference plane 104 and the vertical reference plane 110 are used together to align the reusable frame 300 in an apparatus where measurements will be taken from an existing modular aperture 200;

[0049] c) a plurality of receiving areas defined by the reference plane, each receiving area being configured to receive a separate module 200, and each area further optionally comprising:

[0050] A window or opening 302 for allowing the device to measure samples contained within individual modules;

[0051] d) at least one vertically oriented registration feature 112 for aligning each individual module 200 relative to the vertical reference plane 110; and,

[0052] e) at least one horizontally oriented registration feature 108 , the at least one vertically oriented registration feature used to align each individual module 200 relative to the horizontal reference plane 104 .

[0053] In another aspect, a reference plane refers to a datum plane (eg, a wall) used as a reference position for alignment of a modular well plate system (specifically a floor section) with a desired device (or machine or instrument as used interchangeably herein).

[0054] In another aspect, examples of the plurality of receiving areas include dimples, depressions, and grooves or other features (not numbered).

[0055] Another aspect relates to a novel modular well plate system 100, wherein the reusable frame 300 optionally includes one or more of the following:

[0056] f) at least one registration flexure 306 configured to align the individual modules relative to the vertically oriented registration features 112;

[0057] g) at least one secondary registration flexure 324 configured to align the individual modules relative to the horizontally oriented registration feature 108;

[0058] h) one or more module support flanges 304 configured to align and optionally secure individual modules 200 to a bottom surface of the frame;

[0059] i) an inner ridge 318;

[0060] j) a peripheral ridge 308 configured to cooperate with the internal ridge 318 to contain spills and may be used alone or in combination to support a lid or cover mechanism (not shown);

[0061] k) a centrally located support rib 314 or a plurality of support ribs in a branching structure, the support ribs being configured to provide mechanical support when handling the frame and attaching the module;

[0062] l) the area of ​​the recess 316, which serves to capture spilled sample or to serve as a basis for mechanical attachment of a lid or cover mechanism;

[0063] m) introducing feature 320;

[0064] n) origin indicator 102;

[0065] o) a coordinate system 106 for identifying individual modules;

[0066] p) an area 312 designated for placement of a company logo or an inscribed label for writing or printing experimental information; and,

[0067] q) Rounded corners 322 that allow the frame to fit (or fit more easily) into a variety of multi-microplate readers or similar devices.

[0068] In another aspect, the lead-in feature 320 includes tapered edges to aid in placement and alignment of the module.

[0069] In another aspect, the origin indicator 102 may be used to demonstrate the correct orientation for measurement and analysis.

[0070] In another aspect, the registration flexures 306 and secondary registration flexures 324 align the module with its corresponding registration features 112 and 108, respectively, by applying a directed force. Examples of such force generating flexures include leaf springs, precisely dimensioned features designed to create a press fit, and elastomeric components.

[0071] Another aspect relates to a novel modular well plate system 100, wherein one or more modular wells 200 include:

[0072] a) a plurality of chambers (e.g., 2, 3, 4 or more), each chamber being configured to contain a certain volume (e.g., liquid, reactant, cell, etc.), wherein the plurality of chambers are fastened or connected together (e.g., using a manufacturing method commonly used in the art);

[0073] b) at least one horizontally-oriented registration feature 204 configured to align the module with a corresponding feature 108 on the reusable frame 300; and,

[0074] c) at least one vertically oriented registration feature 206 configured to align the module with a corresponding feature 112 on the reusable frame 300 .

[0075] In another aspect, examples of methods for fastening or connecting the chambers include using self-tapping screws, rivets, adhesives, laser welding, hot stamping, and ultrasonic welding.

[0076] Another aspect relates to a disposable module 200, comprising: a first chamber and a second chamber, and optionally a third or more chambers. Each chamber is configured to contain a certain volume (e.g., a first volume and a second volume). In some aspects, multiple volumes are fluidly connected or connected in pairs in a manner that they can be used to measure interactions that are not related to contact. For example, in Figure 3A and Figure 3B In FIG. 1 , two chambers (not numbered) are shown. In one example, the two chambers include a first volume and a second volume that can be used to measure interactions between different microbial groups separated by a semi-permeable membrane (not shown).

[0077] Another aspect relates to a novel modular well plate system 100, wherein one or more modular wells 200 optionally and independently include one or more of the following:

[0078] d) a top surface 202 to which a lid or other type of sample cover may optionally be attached and aligned;

[0079] e) at least one window or opening 208 for allowing measurement of a sample contained within the chamber;

[0080] f) a bottom surface 210 configured to allow vertical positioning of the module 200 and retention of the module by the support flange 304; and,

[0081] g) At least one alignment feature 212 used during assembly and automation processes for assembling the module 202.

[0082] In another aspect, examples of alignment features 212 include holes for locating pins to allow multiple components to be aligned with each other during assembly.

[0083] refer to Figures 1A to 9 , the modular well plate system 100 , and specifically the reusable frame 300 , is optionally configured to fit a variety of module types (not shown), as long as the outer module dimensions fit into the recesses and alignment features of the reusable frame 300 .

[0084] Another aspect relates to a reusable frame 300 that includes recesses for more than one type and size of disposable modules (not shown). For example, a single frame may contain a mix of recesses or grooves of different sizes to accommodate different combinations of module types (sizes) to perform serial experiments.

[0085] refer to Fig. 6A and Figure 6B One of the benefits of the modular well plate system is that researchers do not need to fill the reusable frame 300 with modules to start an experiment. Only one module is needed to start an experiment. More modules (even different types of modules) can be added during the experiment, or not added at all. This is particularly useful for reducing plastic and material waste and limiting the amount of expensive reagents and / or other chemicals used during experimental discovery and enhancement.

[0086] refer to Figure 1A and Figure 1B , researchers can run all of the different types of assays and sample modules contained in the same modular well plate system 100. Additionally, if experiments with a given module (or modules) fail to produce the desired results, researchers can replace the module (or modules) with another module of a different type or composition.

[0087] Another aspect relates to a modular well plate system in which the module chambers match the volume and spacing of standard plate dimensions. Examples of the number of module chambers include 6, 12, 24, 48, 96, and 384.

[0088] In another aspect, the number of chambers present in the modular well plate system ranges from 2-48 (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.

[0089] Another aspect relates to a reusable frame that is configured to allow sterilization after use by autoclave, ethylene oxide gas treatment, or other treatment standards consistent with laboratory practice. Since the frame and modular well plate system may be used in sensitive environments or in biohazard areas, this type of design consideration will facilitate reuse of frame components.

[0090] Another aspect relates to the opacity of part or all of the walls of the disposable module 200. Fluorescence measurements typically use containers with opaque walls (or, for example, windows in a portion of the wall) so that an optical reading of the sample is taken when the sample begins to glow. For example, a module can be designed for fluorescence so that its parts optically separate the volume of the sample so that their light emissions can be isolated and measured. For example, a fluorescent module can be paired with a non-fluorescent sample to measure contact-independent interactions or protein expression using different types of imaging modalities in a single frame assembly. This can help reduce variables during the experimental process, such as timing and environmental control.

[0091] Another aspect relates to a module that is at least partially opaque to facilitate measuring fluorescence of a sample.

[0092] Another aspect relates to a module that is a pair of wells designed to induce a contact-independent interaction between two microbial cultures.

[0093] Another aspect relates to a module that includes a single-well chamber with a rounded or flat bottom, for example, in an unusual size or geometry that is useful for more abstract or novel science.

[0094] Another aspect relates to a module comprising a selective growth substrate. For example, the module is pretreated with a selective growth substrate.

[0095] Another aspect relates to a module that is an artificial sample of standard values ​​for calibration or comparison purposes.

[0096] Another aspect relates to a module that includes a feature having a specific optical density or other parameter comparator for calibrating a device or comparing readouts between different devices.

[0097] Another aspect relates to a module that is a tissue culture treated well designed to promote the growth of adherent cells.

[0098] Another aspect relates to a module that has been pre-treated using a plasma etching process or similar process to promote the growth of cells or microorganisms within the module and / or along the surface of the module. Such a process is sometimes referred to as a tissue culture treatment.

[0099] Another aspect relates to a module that is manipulated to have or contain regions or features that specifically contain or isolate extracellular matrix regions for the purpose of differentiating and / or promoting the growth of different types of eukaryotic cells.

[0100] Another aspect relates to a modular well plate system in which the modules and frame are constructed of materials that are resistant to extreme temperatures and fluctuations. This would be particularly useful when evaluating microorganisms that are classified as extremophiles.

[0101] Another aspect relates to a modular well plate system in which a reusable frame is configured to accommodate nested versions of modules designed to interlock or connect with each other. For example, a large module would act as a slot to hold common metabolites, and other modules would nest into the large module and perform measurements while being constrained by both the geometry of the larger module and the reusable frame.

[0102] Another aspect relates to a module comprising: an independent light source for taking measurements or promoting photosynthetic growth.

[0103] Another aspect relates to a module comprising individual elements and controls designed to actively manage the temperature of the individual modules. This configuration would allow researchers to test the optimal temperature for growing a particular culture.

[0104] All references listed herein are incorporated herein by reference in their entirety. In view of the above teachings, numerous modifications and variations of the present invention are possible. Therefore, it should be understood that within the scope of the appended claims, the present invention may be practiced differently than as specifically described herein.

Claims

1. A modular orifice plate system comprising: a) a plurality of disposable modules, each disposable module comprising: i) at least one chamber; and ii) one or more registration features; and, b) a reusable framework, the reusable framework comprising: i) at least one horizontal reference plane; ii) at least one vertical reference plane; iii) a plurality of receiving areas defined by the reference plane, each receiving area being configured to receive one module from the plurality of modules; iv) one or more registration features corresponding to the one or more registration features on the module; in: The modules described are configured individually for experimental purposes; The modules are temporarily adhered to the frame via respective registration features of each module; and The frame is configured to mate with a standard multiwell plate reader and present the temporarily attached modules for measurement.

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

3. The well plate system of claim 1, wherein the module is presented at a horizontal position corresponding to the horizontal position of one or more wells of a standard multi-well plate. 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. The well plate system of claim 1, wherein at least one module is a well pair designed to induce a contact-independent interaction between two microbial cultures.

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

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

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

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

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

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

14. The orifice plate system of claim 1, wherein at least one module is constructed of a material resistant to extreme temperatures.

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

16. The well plate system of claim 1, wherein at least one module further comprises: A light source is used to perform the measurement.

17. The well plate system of claim 1, wherein at least one module further comprises: A light source is used to promote photosynthetic growth.

18. The well plate system of claim 1, wherein at least one module further comprises: An element designed to actively control the temperature inside the module.

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