Multiwell devices for materials characterization, related apparatuses and associated methods

Abstract

The following description generally relates to techniques, devices, apparatuses, and methods used for screening and characterizing a plurality of samples within an experimental run by X-ray diffraction (XRD) experiments in which it may be useful to investigate a relatively large number of samples, several samples in situ, sequentially and / or simultaneously. The present disclosure concerns a multiwell device allowing, for example and without being limitative, high-throughput screening and in-situ characterization of materials which can be investigated using XRD-based techniques. The screening achievable using the technology that will be herein described does not require the time-consuming step of removing the material or the sample during an experiment, and is also compatible with various analytical techniques, which include but are not limited to the XRD-based techniques mentioned above. Another example of such analytical techniques includes spectroscopic methods (e.g., infrared spectroscopy or fluorescence- based screening techniques).

Description

[0001] MULTIWELL DEVICES FOR MATERIALS CHARACTERIZATION, RELATED APPARATUSES AND ASSOCIATED METHODS

[0002] TECHNICAL FIELD

[0003] The technical field generally relates to the field of analytical techniques. More particularly, it relates to multiwell devices for materials synthesis and characterization, related apparatuses, and associated methods.

[0004] BACKGROUND

[0005] There is a need for improved techniques, devices, apparatuses, and methods for X-ray diffraction experiments which allow investigating large numbers of samples.

[0006] SUMMARY

[0007] In accordance with one aspect, there is provided a method for characterizing a plurality of samples using an analytical technique in a single experimental run, the method including at the beginning of the experimental run, providing a sample of the plurality of samples in each well of a plurality of wells of a multiwell device; for each sample of the plurality of samples: mixing the sample to start or promote the reaction within the well, the sample covering a reaction surface of the well after the reaction; and once the reaction is complete, characterizing the reaction surface of the well, using the analytical technique, wherein the experimental run ends when all the samples of the plurality of samples have been characterized.

[0008] In some embodiments, mixing the sample includes a solid mixing.

[0009] In some embodiments, mixing the sample includes a liquid-assisted mixing.

[0010] In some embodiments, mixing the sample includes a resonant acoustic mixing.

[0011] In some embodiments, mixing the sample includes a liquid-assisted resonant acoustic mixing. In some embodiments, mixing the sample includes grinding the sample with a mixing media.

[0012] In some embodiments, the method further includes including adding the mixing media to the corresponding well.

[0013] In some embodiments, the mixing media is a metal ring.

[0014] In some embodiments, grinding the sample includes a liquid-assisted grinding.

[0015] In some embodiments, the method further includes heating the sample in the corresponding well.

[0016] In some embodiments, the steps of mixing the sample and heating the sample are performed at the same time.

[0017] In some embodiments, the steps of mixing the sample and heating the sample are performed according to a predetermined sequence.

[0018] In some embodiments, the reaction surface includes a bottom portion of the well.

[0019] In some embodiments, the reaction surface includes a side portion of the well.

[0020] In accordance with one aspect, there is provided a multiwell device for assisting a reaction or a filtration process involving a plurality of samples to be characterized using an analytical technique without the need to remove the plurality of samples from the multiwell device, the multiwell device including: a stack of plates, including: a support plate made from a relatively rigid material containing a plurality of wells in which each well aperture has a flared profile with a chamfered radial exit designed to not obscure or attenuate beams or signals passing through; a substrate or filter plate mechanically connected to the support plate, the substate or filter plate being configured to receive the plurality of samples in regions defined by the plurality of wells of the multiwell device; and at least one additional plate, selected from: a sealing plate to seal the plurality of wells and / or the stack of plates; a substrate or filter plate made from a spectroscopically transparent material and configured to catch material falling thereon; an extension plate including extension apertures aligned with the plurality of wells, such that the volume of each well is increased when the extension plate is placed above the plurality of wells; a housing plate sized and configured to receive at least one plate forming the multiwell device; a collection plate including a plurality of receptacles, each receptacle being aligned with a corresponding well; a powder transfer plate configured to secure consecutive plates together to form the multiwell device and / or to operate as a sieve; and a top plate extending over one of the support plate containing a plurality of wells in which each well aperture has a flared profile with a chamfered radial entrance designed to not obscure or attenuate beams or signals passing through, the substrate plate or another one of said at least one additional plate, wherein the stack of plates defines the plurality of wells of the multiwell device, each well having a reaction surface and extending through at least a portion of the stack of plates, each well being adapted for receiving a corresponding sample from said plurality of samples on the reaction surface, such that the corresponding sample can be characterized using the analytical technique when the multiwell device is loaded in an analytical instrument.

[0021] In some embodiments, the reaction surface includes a bottom portion of the well.

[0022] In some embodiments, the reaction surface includes a side portion of the well. In accordance with one aspect, there is provided a filtration multiwell device for characterizing a plurality of samples using an analytical technique, the filtration multiwell device including: a support plate made from a relatively rigid material containing a plurality of wells in which each well aperture has a flared profile with a chamfered radial exit designed to not obscure or attenuate beams or signals passing through; a filter plate extending over the sealing plate and configured to receive the plurality of samples in regions defined by a plurality of wells of the filtration multiwell device, the filter plate being made from a spectroscopically transparent material; a first sealing plate extending over the support plate and a second sealing plate extending over the filter plate, such that the filter plate is sandwiched between the first sealing plate and the second sealing plate, the first sealing plate and the sealing plate being adapted to seal the plurality of wells; and a top plate extending over the second sealing plate containing a plurality of wells in which each well aperture has a flared profile with a chamfered radial entrance designed to not obscure or attenuate beams or signals passing through, wherein the support plate, the filter plate, the first sealing plate, the second sealing plate and the top plate collectively define the plurality of wells of the filtration multiwell device, each well having a reaction surface and extending through at least a portion of the filtration multiwell device, each well being adapted for receiving a corresponding sample from said plurality of samples on the reaction surface, such that the corresponding sample can be characterized using the analytical technique when the filtration multiwell device is loaded in an analytical instrument.

[0023] In some embodiments, the filtration multiwell device further includes a third sealing plate extending over the top plate. In some embodiments, the filtration multiwell device further includes an extension plate extending over the third sealing plate, the extension plate including extension apertures aligned with the plurality of wells, such that the volume of each well is increased when the extension plate is placed above the plurality of wells.

[0024] In some embodiments, the reaction surface includes a bottom portion of the well.

[0025] In some embodiments, the reaction surface includes a side portion of the well.

[0026] In accordance with one aspect, there is provided a reactor multiwell device for characterizing a plurality of samples using an analytical technique, the reactor multiwell device including: a support plate made from a relatively rigid material containing a plurality of wells in which each well aperture has a flared profile with a chamfered radial exit designed to not obscure or attenuate beams or signals passing through; a first substrate plate mechanically connected to the support plate, the first substate plate being configured to receive the plurality of samples in regions defined by a plurality of wells of the multiwell device; a sealing plate extending over the first substrate plate; a second substrate plate extending over the sealing plate, such that the sealing plate is sandwiched between the first substrate plate and the second substrate plate; and a top plate extending over the second substrate plate containing a plurality of wells in which each well aperture has a flared profile with a chamfered radial entrance designed to not obscure or attenuate beams or signals passing through, wherein the support plate, the sealing plate, the first substrate plate, the second substrate plate and the top plate collectively define the plurality of wells of the reactor multiwell device, each well having a reaction surface and extending through at least a portion of the reactor multiwell device, each well being adapted for receiving and containing a corresponding sample from said plurality of samples on the reaction surface, such that the corresponding sample can be characterized using the analytical technique when the reactor multiwell device is loaded in an analytical instrument.

[0027] In some embodiments, the reaction surface includes a bottom portion of the well.

[0028] In some embodiments, the reaction surface includes a side portion of the well.

[0029] In accordance with one aspect, there is provided a crystallization multiwell device for characterizing a plurality of samples using an analytical technique, the crystallization multiwell device including: a support plate made from a relatively rigid material containing a plurality of wells in which each well aperture has a flared profile with a chamfered radial exit designed to not obscure or attenuate beams or signals passing through; a substrate plate mechanically connected to the support plate, the substate plate being configured to receive the plurality of samples in regions defined by a plurality of wells of the multiwell device; a sealing plate extending over the substrate plate; and a top plate extending over the substrate plate containing a plurality of wells in which each well aperture has a flared profile with a chamfered radial entrance designed to not obscure or attenuate beams or signals passing through, wherein the support plate, the sealing plate, the substrate plate, and the top plate collectively define the plurality of wells of the reactor multiwell device, each well having a reaction surface and extending through at least a portion of the reactor multiwell device, each well being adapted for receiving a corresponding sample from said plurality of samples on the reaction surface, such that the corresponding sample can be characterized using the analytical technique when the reactor multiwell device is loaded in an analytical instrument.

[0030] In some embodiments, the crystallization multiwell device further includes a second sealing plate extending over the top plate. In some embodiments, the crystallization multiwell device further includes an extension plate extending over the second sealing plate, the extension plate including extension apertures aligned with the plurality of wells, such that the volume of each well is increased when the extension plate is placed above the plurality of wells.

[0031] In some embodiments, the reaction surface includes a bottom portion of the well.

[0032] In some embodiments, the reaction surface includes a side portion of the well.

[0033] In accordance with one aspect, there is provided a micronizing multiwell device for characterizing a plurality of samples using an analytical technique, the micronizing multiwell device including: a housing plate; a first sealing plate extending within the housing plate; a collection plate extending over the first sealing plate and including a plurality of receptacles, each receptacle being aligned with a corresponding well of a plurality of wells of the micronizing multiwell device; a second sealing plate extending over the collection plate; a support plate made from a relatively rigid material containing a plurality of wells; a substate plate extending over the support plate; and a powder transfer plate configured to secure consecutive plates together to form the multiwell device and / or to operate as a sieve, wherein the plates defines the plurality of wells of the micronizing multiwell device, each well having a reaction surface and extending through at least a portion of the plates, each well being adapted for receiving a corresponding sample from said plurality of samples on the reaction surface, such that the corresponding sample can be characterized using the analytical technique when the micronizing multiwell device is loaded in an analytical instrument.

[0034] In some embodiments, the reaction surface includes a bottom portion of the well. In some embodiments, the reaction surface includes a side portion of the well.

[0035] In accordance with one aspect, there is provided a micronizing multiwell device for characterizing a plurality of samples using an analytical technique, the micronizing multiwell device including: a housing plate; a first sealing plate extending within the housing plate; a collection plate extending over the first sealing plate and including a plurality of receptacles, each receptacle being aligned with a corresponding well of a plurality of wells of the micronizing multiwell device; a second sealing plate extending over the collection plate; a powder transfer plate extending over the second filter plate and configured to secure consecutive plates together to form the multiwell device and / or to operate as a filter; a third sealing plate extending over the powder transfer plate; a support plate made from a relatively rigid material containing a plurality of wells; and a substate plate extending over the support plate, wherein the plates define the plurality of wells of the micronizing multiwell device, each well having a reaction surface and extending through at least a portion of the plates, each well being adapted for receiving a corresponding sample from said plurality of samples therein, such that the corresponding sample can be characterized using the analytical technique when the micronizing multiwell device is loaded in an analytical instrument.

[0036] In some embodiments, the reaction surface includes a bottom portion of the well.

[0037] In some embodiments, the reaction surface includes a side portion of the well.

[0038] In accordance with one aspect, there is provided a multiwell device for assisting a reaction or a filtration process involving a plurality of samples to be characterized using an analytical technique without the need to remove the plurality of samples from the multiwell device, the multiwell device including: a stack of plates, including: a support plate made from a relatively rigid material containing a plurality of wells in which each well aperture has a flared profile with a chamfered radial exit designed to not obscure or attenuate beams or signals passing through; a substrate or filter plate mechanically connected to the support plate, the substate or filter plate being configured to receive the plurality of samples in regions defined by the plurality of wells of the multiwell device; and at least one additional plate, selected from: a sealing plate to seal the plurality of wells and / or the stack of plates; a substrate or filter plate made from a spectroscopically transparent material and configured to catch material falling thereon; an extension plate including extension apertures aligned with the plurality of wells, such that the volume of each well is increased when the extension plate is placed above the plurality of wells; a housing plate sized and configured to receive at least one plate forming the multiwell device; a collection plate including a plurality of receptacles, each receptacle being aligned with a corresponding well; a powder transfer plate configured to secure consecutive plates together to form the multiwell device and / or to operate as a sieve; and a top plate extending over one of the support plate containing a plurality of wells in which each well aperture has a flared profile with a chamfered radial entrance designed to not obscure or attenuate beams or signals passing through, the substrate plate or another one of said at least one additional plate, wherein the stack of plates defines the plurality of wells of the multiwell device, each well extending through at least a portion of the stack of plates and being adapted for receiving a corresponding sample from said plurality of samples therein, such that the corresponding sample can be characterized using the analytical technique when the multiwell device is loaded in an analytical instrument.

[0039] In accordance with one aspect, there is provided a filtration multiwell device for characterizing a plurality of samples using an analytical technique, the filtration multiwell device including: a support plate made from a relatively rigid material containing a plurality of wells in which each well aperture has a flared profile with a chamfered radial exit designed to not obscure or attenuate beams or signals passing through; a filter plate extending over the sealing plate and configured to receive the plurality of samples in regions defined by a plurality of wells of the filtration multiwell device, the filter plate being made from a spectroscopically transparent material; a first sealing plate extending over the support plate and a second sealing plate extending over the filter plate, such that the filter plate is sandwiched between the first sealing plate and the second sealing plate, the first sealing plate and the sealing plate being adapted to seal the plurality of wells; and a top plate extending over the second sealing plate containing a plurality of wells in which each well aperture has a flared profile with a chamfered radial entrance designed to not obscure or attenuate beams or signals passing through, wherein the support plate, the filter plate, the first sealing plate, the second sealing plate and the top plate collectively define the plurality of wells of the filtration multiwell device, each well extending through at least a portion of the filtration multiwell device and being adapted for receiving a corresponding sample from said plurality of samples therein, such that the corresponding sample can be characterized using the analytical technique when the filtration multiwell device is loaded in an analytical instrument.

[0040] In some embodiments, the filtration multiwell further includes a third sealing plate extending over the top plate.

[0041] In some embodiments, the filtration multiwell further includes an extension plate extending over the third sealing plate, the extension plate including extension apertures aligned with the plurality of wells, such that the volume of each well is increased when the extension plate is placed above the plurality of wells.

[0042] In accordance with one aspect, there is provided a reactor multiwell device for characterizing a plurality of samples using an analytical technique, the reactor multiwell device including: a support plate made from a relatively rigid material containing a plurality of wells in which each well aperture has a flared profile with a chamfered radial exit designed to not obscure or attenuate beams or signals passing through; a first substrate plate mechanically connected to the support plate, the first substate plate being configured to receive the plurality of samples in regions defined by a plurality of wells of the multiwell device; a sealing plate extending over the first substrate plate; a second substrate plate extending over the sealing plate, such that the sealing plate is sandwiched between the first substrate plate and the second substrate plate; and a top plate extending over the second substrate plate containing a plurality of wells in which each well aperture has a flared profile with a chamfered radial entrance designed to not obscure or attenuate beams or signals passing through, wherein the support plate, the sealing plate, the first substrate plate, the second substrate plate and the top plate collectively define the plurality of wells of the reactor multiwell device, each well extending through at least a portion of the reactor multiwell device and being adapted for receiving and containing a corresponding sample from said plurality of samples therein, such that the corresponding sample can be characterized using the analytical technique when the reactor multiwell device is loaded in an analytical instrument.

[0043] In accordance with one aspect, there is provided a crystallization multiwell device for characterizing a plurality of samples using an analytical technique, the crystallization multiwell device including: a support plate made from a relatively rigid material containing a plurality of wells in which each well aperture has a flared profile with a chamfered radial exit designed to not obscure or attenuate beams or signals passing through; a substrate plate mechanically connected to the support plate, the substate plate being configured to receive the plurality of samples in regions defined by a plurality of wells of the multiwell device; a sealing plate extending over the substrate plate; a top plate extending over the substrate plate containing a plurality of wells in which each well aperture has a flared profile with a chamfered radial entrance designed to not obscure or attenuate beams or signals passing through, wherein the support plate, the sealing plate, the substrate plate, and the top plate collectively define the plurality of wells of the reactor multiwell device, each well extending through at least a portion of the reactor multiwell device and being adapted for receiving a corresponding sample from said plurality of samples therein, such that the corresponding sample can be characterized using the analytical technique when the reactor multiwell device is loaded in an analytical instrument.

[0044] In some embodiments, the filtration multiwell further includes a second sealing plate extending over the top plate.

[0045] In some embodiments, the filtration multiwell further includes an extension plate extending over the second sealing plate, the extension plate including extension apertures aligned with the plurality of wells, such that the volume of each well is increased when the extension plate is placed above the plurality of wells.

[0046] In accordance with one aspect, there is provided a micronizing multiwell device for characterizing a plurality of samples using an analytical technique, the micronizing multiwell device including: a housing plate; a first sealing plate extending within the housing plate; a collection plate extending over the first sealing plate and including a plurality of receptacles, each receptacle being aligned with a corresponding well of a plurality of wells of the micronizing multiwell device; a second sealing plate extending over the collection plate; a support plate made from a relatively rigid material containing a plurality of wells; a substate plate extending over the support plate; and a powder transfer plate configured to secure consecutive plates together to form the multiwell device and / or to operate as a sieve, wherein the plates define the plurality of wells of the micronizing multiwell device, each well extending through at least a portion of the plates and being adapted for receiving a corresponding sample from said plurality of samples therein, such that the corresponding sample can be characterized using the analytical technique when the micronizing multiwell device is loaded in an analytical instrument.

[0047] In accordance with one aspect, there is provided a micronizing multiwell device for characterizing a plurality of samples using an analytical technique, the micronizing multiwell device including: a housing plate; a first sealing plate extending within the housing plate; a collection plate extending over the first sealing plate and including a plurality of receptacles, each receptacle being aligned with a corresponding well of a plurality of wells of the micronizing multiwell device; a second sealing plate extending over the collection plate; a powder transfer plate extending over the second filter plate and configured to secure consecutive plates together to form the multiwell device and / or to operate as a filter; a third sealing plate extending over the powder transfer plate; a support plate made from a relatively rigid material containing a plurality of wells; and a substate plate extending over the support plate, wherein the plates define the plurality of wells of the micronizing multiwell device, each well extending through at least a portion of the plates and being adapted for receiving a corresponding sample from said plurality of samples therein, such that the corresponding sample can be characterized using the analytical technique when the micronizing multiwell device is loaded in an analytical instrument.

[0048] Other features will be better understood upon reading of embodiments thereof with reference to the appended drawings.

[0049] BRIEF DESCRIPTION OF THE DRAWINGS

[0050] Figures 1 to 15 illustrate various aspects, features, and implementations of, or related to, the present techniques.

[0051] DETAILED DESCRIPTION

[0052] In the following description, similar features in the drawings have been given similar reference numerals. In order to not unduly encumber the figures, some elements may not be indicated on some figures if they were already mentioned in preceding figures. It should also be understood herein that the elements of the drawings are not necessarily drawn to scale, and that the emphasis is instead being placed upon clearly illustrating the elements and structures of the present embodiments.

[0053] The terms “a”, “an” and “one” are defined herein to mean “at least one”, that is, these terms do not exclude a plural number of items, unless stated otherwise. Terms such as “substantially”, “generally” and “about”, that modify a value, condition or characteristic of a feature of an exemplary embodiment, should be understood to mean that the value, condition or characteristic is defined within tolerances that are acceptable for the proper operation of this exemplary embodiment for its intended application. Moreover, it will be appreciated that positional descriptions such as “top”, “bottom”, “under”, “left”, “right”, “front”, “rear”, “adjacent”, “opposite”, “parallel”, “perpendicular”, “inner”, “outer”, “internal”, “external”, and the like should, unless otherwise indicated, be taken in the context of the figures and should not be considered limiting.

[0054] The terms “light” and “optical”, and variants and derivatives thereof, are used to refer to radiation in any appropriate region of the electromagnetic spectrum. The terms “light” and “optical” are therefore not limited to visible light, but can also include, without being limited to, the ultraviolet region and the infrared region of the electromagnetic spectrum. More specifically, in the context of the current disclosure, the terms “X-ray”, “X-radiation”, “light”, “electromagnetic radiation”, “optical”, “spectral profile” “spectral waveband”, derivatives and variants thereof, are used to refer to radiation in any appropriate region of the electromagnetic spectrum. By way of example, the X-rays may cover or substantially correspond to wavelengths ranging from 0.01 to 10 nanometers ( / .e., frequencies in the range of 30 petahertz to 30 exahertz), which may be of particular interest for applications in the materials science industry for investigating the structural (e.g., atomic structure) or mechanical (e.g., residual stress) properties of samples. Also, the skilled person will appreciate that the definition of the spectral ranges, as well as the dividing lines between them, may vary depending on the technical field or the definitions under consideration, and are not meant to limit the scope of applications of the present techniques.

[0055] The terms “sample”, “sample under investigation”, “material”, “analyzed sample”, “powder”, “thin films”, derivatives and variants thereof are used to refer to a quantity of matter extracted or taken apart from a larger amount for analysis, or may refer to matter that is either natural (e.g., a specific chemical element found in nature), synthesized (e.g., a reaction of chemical compounds), or man-made (e.g., a powder formed by scratching a thin film). It will be understood that the sample intrinsically has various physical and chemical properties, which may be assessed using different instruments and methods (e.g., XRD analysis).

[0056] The terms “diffractometer”, “X-ray diffraction apparatus”, “XRD diffraction system”, “powder diffraction instruments”, “X-ray apparatus”, derivatives and variants thereof refer to an apparatus configured to acquire patterns obtained by recording the intensities of X-rays scattered by the sample under investigation at different angles between an incident beam (i.e., X-ray beam incident on the sample) and a scattered beam (also referred to as a “diffracted beam”, a “reflected beam”, or any other similar expressions). The acquired patterns are typically representative of at least one property (e.g., structure) of the material to be inspected. The above- mentioned apparatus could further be understood as a device configured to sense and / or probe x-rays scattered and / or reflected by the surface to be inspected, according to the needs of a particular application. It will be understood that different attachments (also referred to as “external device”, e.g., different kinds of sample holders or the like) may be attached or mounted to the XRD apparatus.

[0057] The XRD apparatus may include an X-ray source (including, for example, a vacuum-sealed X-ray tube or incorporated into a high flux source such as a synchrotron, liquid metal jet, or any other, or any neutron source), an X-ray generator delivering high tension current to the X-ray source, a sample holder to hold the sample to be investigated, an X-ray detector capable of detecting X-ray and / or X-ray photons scattered by the sample and an X-ray optical assembly (typically used for collimating, conditioning, or focusing the X-rays at the detector). The XRD pattern is obtained by recording the intensities of X-rays scattered by the sample at different angles between the beam incident on the sample and beam scattered by the sample.

[0058] Unless stated otherwise, the terms “connected” and “coupled”, and derivatives and variants thereof, refer herein to any structural and / or functional connection or coupling, either direct or indirect, between two or more elements. For example, the connection or coupling between the elements may be acoustical, mechanical, optical, electrical, logical, or any combination thereof. The connection or coupling between two or more elements or components may be temporary or permanent.

[0059] The following description generally relates to techniques, devices, apparatuses, and methods for X-ray diffraction (XRD) experiments in which it may be useful to investigate a relatively large number of samples, several samples in situ, sequentially and / or simultaneously. The present disclosure concerns a multiwell device allowing, for example and without being limitative, high-throughput screening and in-situ characterization of materials which can be investigated using XRD-based techniques. The screening achievable using the technology that will be herein described does not require the time-consuming step of removing the material or the sample during an experiment, and is also compatible with various analytical techniques, which include but are not limited to the XRD-based techniques mentioned above. Another example of such analytical techniques includes spectroscopic methods (e.g., infrared spectroscopy or fluorescencebased screening techniques).

[0060] The multiwell device will sometimes be referred to as a “modular multiwell device” because the components forming the multiwell device according to the present disclosure can be rearranged, reconfigured, and adjusted based on, for example, targeted applications and / or specific requirements that may be associated with a targeted application, or at least some characteristics of the samples under investigation. Each component forming the multiwell device can therefore be seen as a “module”. This modular capability of the multiwell device may be useful in facilitating the screening process of samples being the products of various synthetic methods, which may include, for example and without being limitative: i) reaction crystallization or solvothermal reactions; ii) mechanochemical mixing, including liquid-assisted grinding (LAG); iii) melt crystallization; and iv) solvent evaporation yielding crystalline materials.

[0061] The multiwell device includes a plurality of wells to simultaneously accommodate multiple reaction conditions, number of which depends on the number of individual wells present in the multiwell device. The wells have a reaction surface, which may be embodied by any portions of the wells such as, for example, and without being limitative, a bottom portion or a side portion of the wells. In the embodiments in which the wells have a cylindrical shape, the side portion may correspond to an inner periphery of the well. In some embodiments, the multiwell device may include 24, 48, or 96 wells, as illustrated in the Figures. In some embodiments, the number of reaction conditions matches the number of wells, or alternatively put, the ratio between the number of reaction conditions and the number of wells is 1 : 1 . In these embodiments, the multiwell device may accommodate up to 24, up to 48, or up to 96 reaction conditions (if the multiwell device respectively has 24, 48, or 96 wells, respectively). In some embodiments, several wells may be subjected to the same reaction conditions and / or accommodate similar or identical reaction conditions, as such redundancy may be useful for statistical and / comparison purposes. In these embodiments, the number of reaction conditions does not match the number of wells, or alternatively put, the ratio between the number of reaction conditions and the number of wells is different than 1 :1 (e.g., 1 :2). As a result, in these embodiments, the multiwell device may accommodate less than 24, less than 48, or less than 96 reaction conditions (if the multiwell device respectively has 24, 48, or 96 wells, respectively). It will have been readily understood that the multiwell device may include any number of wells.

[0062] As previously mentioned, the multiwell device is compatible with XRD systems, such as diffractometers, but also with other analytical instruments, such as, for example and without being limitative, spectrometers or other similar instruments. While most of the examples presented in the present description will be made with reference to XRD-based techniques, the multiwell device as presented herein could be compatible with other analytical techniques.

[0063] The multiwell device may facilitate in-situ crystallization, filtration from solution reactions, and mechanochemical reactions using mixer mills or resonant acoustic mixing devices in a format which can then be presented to an instrument for testing / screening. The form factor, dimensions, and general shape of the multiwell device are compatible to be used with robotic handling systems or other similar automated or semi-automated processes. The applications of the multiwell device are numerous and include at least industries working on solid-form pharmaceuticals, perovskites, and thermoelectric materials, among others. As previously mentioned, the multiwell device includes a plurality of components or modules. The components or modules are shaped and configured to be positioned in a stacked configuration one with respect to the others, and their dimensions can be standardized. Each component or module is a layer included in the stack, and this stack of coextending and superimposed layers collectively form the multiwell device. Of note, each component or module serves at least one specific or predetermined function.

[0064] The technology and its advantages will become more apparent from the detailed description and examples that follow, which present the various embodiments of the technology. More particularly, the following sections of the description will present different embodiments of multiwell devices for materials characterization, related apparatuses, and associated methods.

[0065] In accordance with one aspect, and with reference to Figure 14, there is provided a method 200 for characterizing a plurality of samples using an analytical technique in a single experimental run. The method includes, at the beginning of the experimental run, a step 202 of providing a sample of the plurality of samples in each well of a plurality of wells of a multiwell device. The multiwell device may be embodied by one of the configurations having been previously described. The method 200 also includes, for each sample of the plurality of samples, a step 204 mixing the sample to start or promote the reaction within the well, such that the sample covers a reaction surface of the well after the reaction, The method 200 also includes, once the reaction is complete, a step 206 of characterizing the reaction surface of the well, using the analytical technique, wherein the experimental run ends when all the samples of the plurality of samples have been characterized. It should be noted that the expression “single experimental run” may encompass different scenarios, such as, for example: i) whether the sample is enclosed within a device to perform a reaction between two polymer “windows” ; ii) after a filtration process; and iii) after micronization as sample does not need to be removed as all samples are transferred to the XRD transfer plate as part of the method.

[0066] In some embodiments, mixing the sample includes a solid mixing. In some embodiments, mixing the sample includes a liquid-assisted mixing. In some embodiments, mixing the sample includes a resonant acoustic mixing. In some embodiments, mixing the sample includes a liquid-assisted resonant acoustic mixing. In some embodiments, mixing the sample includes grinding the sample with a mixing media. In some embodiments, the method further includes including adding the mixing media to the corresponding well. In some embodiments, the mixing media is a metal ring. In some embodiments, grinding the sample includes a liquid-assisted grinding. In some embodiments, the method further includes heating the sample in the corresponding well. In some embodiments, the steps of mixing the sample and heating the sample are performed at the same time. In some embodiments, the steps of mixing the sample and heating the sample are performed according to a predetermined sequence. In some embodiments, the reaction surface includes a bottom portion of the well. In some embodiments, the reaction surface includes a side portion of the well.

[0067] With reference to Figures 1 to 13, different embodiments of a multiwell device 100, 120, 140, 160 and 180 and components thereof will be presented. It should be noted that the multiwell device 100, 120, 140, 160 and 180 minimally includes a stack including of plurality of plates 110A,B,... , N, 130A,B, ... , N, 150A,B, ... , N, 170A,B, ... ,N, 190A,B,... ,N, wherein / V represents the nthplate of the stack. The stack includes at least a support plate and a sealing plate, in addition to at least one other plate selected from: a substrate plate, a filter plate, a top plate, an extension plate, a housing plate, a collection plate, and a powder transfer plate. Depending on the arrangement and configuration of these plates, multiwell devices 100, 120, 140, 160 and 180 with different functions and capabilities can be designed and manufactured. The function(s) achieved by the multiwell devices 100, 120, 140, 160 and 180 can be grouped into different “types” or “classes” of multiwell devices 100, 120, 140, 160 and 180. Nonlimitative examples of types of multiwell devices 100, 120, 140, 160 and 180 will be presented later.

[0068] Characteristics and properties of each of the plates 110A, B, ... ,N, 130A,B, ... , N, 150A,B, ... , N, 170A,B, ... , N, 190A,B, ... , N, listed above will now be described in greater detail.

[0069] Each embodiment of the multiwell device 100, 120, 140, 160 and 180 may include any number of well(s) 102.

[0070] The support plate provides support for the other plates or layers included in the multiwell device. The properties of the support plate, which may include, to name a few, dimensions, size, flexibility, rigidity, and composition, are such that it acts as a relatively solid structure for the other plates forming the multiwell device. In some embodiments, the support plate may include threaded holes through which screws or other fasteners can be inserted to secure the support plate to the other plate(s). In some embodiments, the support plate can be the bottom piece of the multiwell device. In these embodiments, the support plate will be referred to as the “bottom plate”. In other embodiments, the support plate may be positioned elsewhere in the multiwell device, which can be useful when a relatively rigid layer or additional support is needed somewhere in stack of layers forming the multiwell device. In some embodiments, the support plate is made of metal or an alloy material. Nonlimitative examples of appropriate materials are stainless steel, titanium, or high-strength aluminum. In other embodiments, the support plate is made of plastic, such as, for example, high-strength plastic. In yet other embodiments, the support plate is made of a ceramic material, or a ceramic-based material. As shown in the Figures, the support plate includes a plurality of apertures. The number of apertures corresponds to the number of wells being formed by the superimposition of the plates which have been previously listed. In some embodiments, the support plate has 24 apertures formed therein, meaning that the multiwell device - once assembled - includes 24 wells. In other embodiments, the support plate has 48 apertures and the multiwell device includes 48 wells. In yet other embodiments, the support plate has 96 apertures and the multiwell device includes 96 wells. In yet other embodiments, the support plate has 384 apertures and the multiwell device includes 384 wells. Of note, the support plate may include any number of apertures, as long as the number of apertures matches the number of apertures provided in the other plates to form the wells of the multiwell device. As previously mentioned, the support plate can be fastened or secured to the other plates of the multiwell plate using a combination of threaded holes and screws. Other fastening mechanisms could also be contemplated, such as, for example, and without being limitative, pins, snaps and / or magnets.

[0071] Each of the apertures of the support plate has a profile or a geometry optimizing or facilitating a passage of the interrogating beam of electromagnetic radiation, which may be, in some embodiments, an X-ray beam. In the illustrated embodiments, each aperture has a circular cross-section and is flared with a chamfered radial exit, which allows a relatively large diffraction angle. Such a large diffraction angle is useful to not obscure or attenuate the signal exiting the multiwell device after its passage through a given well ( / .e., the diffracted X-ray beam, when the interrogating beam is an X-ray beam). The length, the width and the thickness of the support plate, as well as the diameter and the angle of chamfer of the apertures formed in the support plate are selected to allow maximum XRD signal.

[0072] Substrate The substrate plate will now be described. As previously mentioned, the substrate plate is optional, and is only included in some types or classes of multiwell devices. When the substrate plate is present in the stack of plates forming the multiwell device, the substrate plate is configured to receive a sample thereon deposited, so as to act as the substrate for the material under investigation. As the signal emanating from the material forming the sample needs to be collected, the substrate plate should be made from a spectroscopically transparent material. In some embodiments, the spectroscopically transparent material is also amorphous, so as to minimize the generation of an additional XRD signal which would not be representative of the sample under investigation. In some embodiments, the substrate plate is made of solid plastic, such as Kapton polyimide. Advantages of such a material is its relatively high-temperature operating range of about 400°C, and its relatively high-tensile strength of about 33,500 psi. In some embodiments, the substrate plate is made from polyester or polyethylene. In these embodiments, an adhesive can be provided on one surface of the substrate plate to facilitate or promote adhesion of powdered samples. The presence of adhesive however limits the temperature operating range to about 150°C. Similarly to the support plate, the substrate plate can be fastened or secured to the other plates of the multiwell plate using a combination of threaded holes and screws. Other fastening mechanisms could also be contemplated. In some embodiments, the substrate plate has a thickness of about 0.001 inch or about 25 microns.

[0073] Sealing plate (part C)

[0074] Another layer of the multiwell device is the sealing plate. In some embodiments, the sealing plate is made of silicone, or a rubber / silicone blend. As its name entails, the sealing plate acts as a sealing gasket between the components forming the multiwell device. The sealing plate prevents the leakage of the sample, or a portion thereof, which may include powders, liquids, or any combinations thereof between the stack of layers forming the multiwell device. The sealing plate can operate up to a high-temperature range of about 220°C and a tensile strength up to about 1 ,200 psi. In some embodiments, the sealing plate has a medium Durometer of about 50A. In some embodiments, the sealing plate is made of rubber. In some embodiments, the sealing plate has 24 apertures formed therein. In other embodiments, the sealing plate has 48 apertures. In yet other embodiments, the sealing plate has 96 apertures. As for the support plate, the sealing plate may include any number of apertures, as long as the number of apertures matches the number of apertures provided in the other plates to form the wells of the multiwell device. Similarly to the support plate, the sealing plate can be fastened or secured to the other plates of the multiwell plate using a combination of threaded holes and screws. Other fastening mechanisms could also be contemplated.

[0075] In some embodiments, the sealing plate or at least a portion thereof forms a sidewall or sidewalls of the wells. Of note, the thickness of the sealing plate will determine the working volume of each well defined within the sidewall(s). In some embodiments, both the upper surface and the lower surface of the sealing plate are substantially planar. In other embodiments, at least one of the upper surface and the lower surface of the sealing plate includes a plurality of protrusions extending in a direction that is not parallel to the upper surface and / or the lower surface. Each protrusion follows a periphery of a corresponding well and is shaped and sized to be inserted in apertures of plate(s) contiguous to the sealing, and / or any other

[0076] Filter

[0077] Another component of the multiwell device is the filter plate. The filter plate is preferably a thin filter and is configured to catch material that is deposited on or that has been placed on this layer. The filter plate serves as a porous substate, and any signal emanating from the filter plate, including the material forming the same, will be collected, so the material from which is made the filter plate should be spectroscopically transparent. In some embodiments, the spectroscopically transparent material forming the filter plate is also amorphous, so as to minimize the generation of an additional XRD signal which would not be representative of the sample under investigation. In some embodiments, the filter plate is made of a porous plastic such as polyester or nylon. In some embodiments, the filter plate has a mesh size of 500x500, or about 25 microns. In some embodiments, the filter plate has a pore size comprised between about 1 to 50 microns. In some embodiments, the filter plate has a thickness comprised between about 0.001 to 0.002 inches ( / .e., about 25 to about 50 microns).

[0078] Another optional component of the multiwell device is the top plate. When present in the multiwell device, the top plate is typically the top piece of the device, unless the multiwell device is capped with a housing or other components, as it will be explained in greater detail below. In some embodiments, the top plate is made of metal or an alloy. Examples of the material forming the top plate are stainless steel, titanium and high-strength aluminum. In some embodiments, the top plate has 24 apertures formed therein. In other embodiments, the top plate has 48 apertures. In yet other embodiments, the top plate has 96 apertures. As for the other plates or components including apertures, the top plate may include any number of apertures, as long as the number of apertures matches the number of apertures provided in the other plates to form the wells of the multiwell device. Similarly to the other plates, the top plate can also be fastened or secured to the other plates of the multiwell plate using a combination of threaded holes, non-threaded holes, magnets, pins, and screws. Other fastening mechanisms could also be contemplated. Now turning to the geometry of the top plate, each aperture has flared profile with a chamfered radial entrance design to allow for not blocking any incoming beams or signals, such as the ones emanating from a camera or laser that is used for targeting. The largest entrance angle possible can be used to not obscure the imaging of the sample under investigation, and the X-ray beam (or light beam) can be used to investigate the properties of the materials disposed in the wells. An additional fastening mechanism may be provided to secure an extension, a housing or a cap to the multiwell device. The additional fastening mechanism may include threaded screw holes or magnets.

[0079] Extension

[0080] As mentioned above, the multiwell device may include, in some embodiments, an extension plate. The presence of the extension plate in the stack of plates forming the multiwell device increases the volume of the wells. The thickness of the extension plate is such that it increases the length of the wells formed in the other layers or plates of the multiwell device. In some embodiments, the extension plate may be secured, fixed, or attached to the top plate. The increase in volume resulting from the addition of the extension plate to the multiwell device may be useful when larger amounts of liquid for filtration or crystallization need to be transferred to the multiwell device. In some embodiments, the extension plate is made from a metal or an alloy, such as, for example and without being limitative, stainless steel, titanium or high-strength aluminum. In some embodiments, the extension plate may be made from a high-strength plastic or a ceramic. The number of apertures present in the extension plate depends on the number of apertures defined in the layers or plates provided below the extension plate. For instance, if the multiwell device includes 24 wells, the extension plate may include 24 wells. If the multiwell device includes 48 wells, the extension plate may include 48 wells. If the multiwell device includes 96 wells, the extension plate may include 96 wells. In some embodiments, the number of apertures present in the extension plate may be less than the number of wells present in the multiwell device, which could be useful if only a selected number of wells need an additional volume. The extension plate can be attached, secured or fastened to the other plates using the fastening mechanism previously described.

[0081] Housing plate (part G)

[0082] In some embodiments, the multiwell device may include a housing plate. The housing plate may include a depression which allows receiving at least one other plate or layer forming the multiwell device. The housing plate may include inner walls to ensure a proper alignment between all the components of the multiwell device. As for the other plates described above, the housing plate may be made from metal or an alloy. Examples of the material forming the top plate are stainless steel, titanium and high-strength aluminum. Collection

[0083] Another optional component of the multiwell device is the collection plate. The collection plate may be embodied by a plastic plate including a plurality of receptacles, positioned to be aligned with the wells of the multiwell device. In some embodiments, the collection plate includes 24 receptacles. In other embodiments, the collection plate includes 48 receptables. In yet other embodiments, the collection plate includes 96 receptacles. The volume of each receptacle present in the collection plate may vary. Examples of a useful volume for such a receptacle is about 355 microliters, 500 microliters, or up to 2 mL.

[0084] Powder transfer

[0085] The multiwell device may include a powder transfer plate. The powder transfer plate has two main functions: i) to secure the plates together to form the multiwell device, and ii) to operate as a sieve, or in other words as a powder transfer plate to prevent the circulation of an undesired material of a larger size toward other plates of the multiwell devices. A nonlimitative example of such an undesired material would be micronizing balls in the support plate. The lower part of the powder transfer plate may match the dimensions of the plate provided below the powder transfer plate. The upper part of the powder transfer plate may match the dimensions of the plate(s) provided above the powder transfer plate. The powder transfer plate may be secured or attached to other plate(s) of the multiwell device using the fastening mechanism previously presented. In some embodiments, the powder transfer plate may include small openings to allow the passage of powder but not to allow the passage of micronizing or grinding balls that may have been used.

[0086] Now that embodiments of the plates that may be included in the multiwell device have been described, nonlimitative examples of multiwell devices, each including different combinations and / or arrangements of the plate will be presented.

[0087] A first type or class of multiwell devices are filtration multiwell devices. The utility of the filtration multiwell device allows for many solid samples dispersed in solution (e.g., 24, 48, and 96) to be filtered simultaneously. The solids dispersed in solution can be transferred to through the top of the completely assembled device and allowed to gravity filter or can be speed up by placing on a vacuum filtration apparatus. The multiwell device then can be transferred directly to an analytical instrument such as a transmission X-ray diffractometer for analysis without the need for further transfer of material. This significantly increases the throughput and speed of sample preparation needed for analysis, allowing for high throughput screening of samples. The filtration multiwell device is constructed to ensure that the X-ray signal is not obstructed by the chamfered edges of the multiwell plate entrance and exit. The filter material also has the correct pore size to retain a high proportion of the dispersed solids and also is sufficiently thin / amorphous to result in minimal background signal. Because the filtration multiwell device can be directly transferred to an XRD instrument for transmission or reflection XRD measurements, the sample preparation time is reduced. It also reduces sample handling which could result in sample loss during transfer of individual sample. It also reduces the chance for contamination between samples and is particularly useful when dealing with highly toxic samples in which you want to reduce transfer steps and unnecessary handling of the material.

[0088] A second type or class of multiwell devices are reactor multiwell devices. The reactor multiwell device allows for several solid-state reactions to occur simultaneously via mixing / heating and for the samples to be analyzed through the Kapton windows of the substrate plate without having to transfer the solid out or open the device. The reaction may occur from the mixture of one or more solid samples with or without small catalytic amounts of solvent and heating of the entire device. The entire device can be placed in an oven and heated to 200°C to allow for melting of one or more of the solids which facilities the creation of new solid forms. It can also be mixed before, during, or after heating to further facilitate the materials conversion.

[0089] The operation of this class of multiwell devices will now be presented. Solids are placed in the wells once the support plate, the substrate plate and the sealing plate have been assembled. Another substrate plate is then secured to the top plate. The substrate plate, above and below, behaves as a bottom and top of a sealed vessel (sealed with Kapton), with the walls formed by the sealing plate, behaving as the vessel sides (made from silicone / rubber). The device can then be placed in an oven to induce melt crystallization between different solids and / or placed in a mixing device such as a resonant acoustic mixer. Then the entire device can be transferred to an analytical instrument such as an X-ray diffraction instrument and the samples analyzed without opening the device.

[0090] The reactor multiwell device allows for samples to be mixed and heated (possibly melted) when placed between two Kapton sheets with a silicon rubber gasket behaving as the walls of the vessel. This allows for chemical reaction or new solid phases to form during heating and mixing (mixing can occur via a resonant acoustic mixing device). After the reaction, the samples can be analyzed without having to be removed from the device, saving significant time, reducing loss of material during transfer, and increasing the overall speed of materials discovery. This can be particularly advantageous when working with highly toxic or reactive components that may react with air, as the samples can be sealed and still be analyzed through the windows of the device. Within this device, new materials could form upon i) dry mixing of solids via mechanochemical means, ii) solvent assisted mechanochemistry via additions of microliters of liquids, iii) some combination of i or ii with the use of heating, particularly when compounds can be melted as it takes away the compounds lattice energy reducing the activation energy required for compounds to react and form new solid forms, such as pharmaceutical co-crystals containing a pharmaceutical and a co-former.

[0091] A third type or class of multiwell devices are crystallization multiwell devices. This class of devices allows for the evaporation of solvent and subsequent crystallization onto the substrate plate. This allows for many samples to be crystalized and subsequently analyzed directly without requiring transfer of the solid to another sample holder. The ability to exchange the substrate plate allows for ways to induce the formation of alternative crystal forms, such as polymorphs. By altering the wettability / surface energy or to alter the patterning / morphology of the surface one has the ability to induce the formation of different crystal habits, shapes, or even polymorphs. The extension plate used in this class of multiwell devices allows for larger volumes to be used and subsequently removed once the solvent has evaporated. In some embodiments, a grinding step may be required to grind large single crystals to a polycrystalline powder if powder X-ray diffraction is the desired analytical screening tool. This can be accomplished by placing the entire device into a mixing machine such as a resonant acoustic mixer. This class of multiwell devices allows for many samples to be evaporated / crystallized within a single device and subsequent analysis without having to transfer the material out of the device to a secondary analysis microplate. The crystallization multiwell devices allow one to easily swap the substrate and replace Kapton with a different polymer / material with different wettability (surface energy) or pattering to induce crystallization of different polymorphs, or different crystal habit (shapes) or size. The addition and easy removal of the extension plate allows one to work with larger volumes of solvent but still have the final material crystallized within an intact device. While other crystallization plates exist that allow for the evaporation of solids, these devices do not allow for direct transfer of the intact device to an instrument for analysis. In other commercially available products, compounds can be evaporated onto a thick glass substrate which must be disassembled from the device for subsequent reflection XRD analysis.

[0092] A fourth type or class of multiwell devices are micronizing multiwell devices. The micronizing multiwell devices allow disposable plastic multiwell plates (with solids, liquids and mixing media, such as balls) to be placed within and sealed in a device so that mechanochemical reactions can proceed within the multiwell device once the entire assembly is placed in a mixing device. Afterwards, there is a methodology to cleanly transfer the solid contents of those wells to a new multiwell device for XRD or spectroscopic analysis, leaving behind the mixing media. This class of multiwell devices allows plastic well plates with a variety of wells (24,48,96) of the collection plate to be loaded within a cavity of the housing plate and sealed within the device. As mentioned above, this configuration allows for larger volumes, included in a range extending from about 0.0005 mL to about 2 mL for a 96 multiwell device. Larger volumes such as about 4 to about 8 mL could be accommodated in a 24 multiwell device. The larger volume allows the well plate to accommodate larger amounts of solids, liquids, and room for mixing media such as ball bearings made of metal or zirconia. The materials can then be mixed under mechanochemical conditions using a mixer mill or resonant acoustic mixer. Under these conditions, new solid-state materials can form and they can be subsequently transferred with the device to a plate that can be transferred to an XRD instrument (or other analytical instrument) for analysis. The operation of a multiwell device according to this class of devices will now be presented. In a first step, the part C (solid rubber matt with no holes) is inserted within the cavity of part G. Part H is placed inside. Within part H, the solids, liquids, and mixing media (balls) would have already been placed inside the wells (this can be accomplished by using robotic solid / liquid dispensing systems). Then, a solid rubber mat (version of part C with no holes) can be placed on top, followed by the solid lid (part I) which encloses the device. The device is transferred to a mechanical mixing device. After mixing the top parts I and C are removed and replaced with a new rubber matt (part C with holes for the wells). A drying step may be used at this point to remove a residual solvent from the device, such as blowing inert nitrogen gas over the multiwell device. In a second step, a solid metal multiwell plate (part A) with part B (Kapton) is joined via a Kapton sheet with adhesive, which also adds adhesive to the substrate in contact with the solids to facilitate transfer. The device is then closed again with part I and sent back to the mixing device, to transfer powder to the top multiwell plate that has wells with an adhesive to stick to the powder. Once mixing is complete the device is taken apart and the multiwell plate (parts A and B) can be transferred to an XRD instrument for analysis. Alternatively, if adhesive Kapton is not used after the first step, part I, which has small holes, can be added to allow for the transfer of powder but not for the transfer of the mixing media (balls inside). Part I is secured to part G via screws or other means. Then parts A, B and C can be added to the top of the device and the entire assembly is placed in a mixing device upside down, to transfer the solid powder from part H through part I into part A with a Kapton (part B) back. After mixing, parts GCHCI are removed from parts A,B,C and parts A and B can be transferred to an XRD instrument (or equivalent analytical device) for XRD analysis. The primary problem addressed with this class of devices is the ability to micronize samples in a multiwell format and transfer that new material or powder to a plate that can analyzed by an analytical instrument such as an X-ray powder diffractometer. Currently, if one is micronizing a sample with mixing media (steel or zirconia balls), it is quite a long process to place the solids, liquids (in some cases), and mixing media in a jar, place in a ball mill, remove jars, scrape solid off mixing media as powered samples often get stuck to balls and jar walls. Existing solutions also include transferring individual solid samples to a plate to run XRD experiments. In the multiwell device according to the present disclosure, the multiwell device has the ability to assist in the reacting of samples under mechanochemical conditions and micronize samples as the mixing occurs within disposable plastic well plates (part H) which are inserted into the device with solids / liquids and mixing media. Upon closure and mechanochemical mixing in a resonant acoustic mixer or other mixer mill the powder can be transferred to a fresh multiwell plate leaving behind the mixing media. The transfer can occur in one of two ways: 1 ) transfer to an adhesive Kapton-backed XRD plate, or 2) transfer of powder through a powder transfer plate with an orifice large enough to let the powder through (3.5mm) but not large enough so the 4 mm or larger balls to be transferred or pass through. The process also allows for drying (evaporation of solvent) and subsequent mixing frees the loose powder off the balls and helps transfer material to the new multiwell plate.

[0093] In accordance with another aspect, there is also provided an XRD apparatus which can be used to characterize samples contained in any one of the embodiments of the multiwell devices described in the current disclosure. The XRD apparatus includes an X-ray source for irradiating the samples - distributed in the wells of the multiwell device - with an X-ray beam. The sample holder of the XRD apparatus may be configured, in some embodiments, to hold or be compatible with the multiwell device herein described. In other embodiments, the multiwell device may act as a sample holder. Notwithstanding the configuration of the sample holder, the samples are positioned to receive the X-ray beam when held by the sample holder. The XRD apparatus also includes a detector for receiving X-rays scattered from the sample and outputting an X-ray diffraction pattern therefrom. The XRD apparatus may include other components, modules and assemblies known from the person skilled in the art.

[0094] In accordance with another broad aspect, there is also provided a method for manufacturing the multiwell device. The multiwell device can be manufactured by assembling, disassembling, adjusting, replacing, removing and adding plates from a stack of plates or layers collectively defining the multiwell device. data

[0095] Figure 14 shows powder X-ray diffraction patterns, and illustrates what happens when a relatively small quantity of carbamazepine and fumaric acid are added to one well of one embodiment of the multiwell reactor device, with a few microliters of solvent MeOH (methanol), both without and with rings.

[0096] The blue pattern shows the XRD pattern of carbamazepine with fumaric acid, prior to mixing in the mutliwell device. Of note, only reflections corresponding to carbamazepine show up in this 2theta range. The green pattern shows what happens upon mixing when placing the multiwell device in a resonant acoustic mixer (RAM). As can be seen, an intermediate phase forms. This intermediate phase is as it closely resembles another literature phase which is a channel structure with oxalic acid. This phase is formed with a lower amount of force applied to the materials in comparison to when rings are added. In effect, the shear forces associated with particle-particle collisions and between layers (gasket and kapton film) of the multiwell device results in this transformation with no mixing media required (i.e. no ring). The red pattern shows the result of adding rings to the multiwell device during mixing. The added ring (mixing media) results in more forces being exerted on the materials inside the well, which is due to material being subjected to higher forces as the ring collides with hard metal top / bottom plate and softer gasket layers of the multiwell device. As a result, the formation of a co-crystal of carbamazepine and fumaric acid is observed, which corresponds to literature pattern (WEYFEN). In summary, the small volume and layered construction of the multiwell device does facilitate the formation of new solid phases (i.e., the intermediate phase in this case but in others co-crystals of carbamazepine can form directly with no mixing media) however, rings help to induce formation of solid phases which take more mechanical force, which is not always obtainable just by mixing in the multiwell device alone. Rings may allow for the formation of more thermodynamic products of reactions, while no rings may allow for the formation of less stable solid forms, which may be kinetic products and have their own useful properties.

[0097] Several alternative embodiments and examples have been described and illustrated herein. The embodiments described above are intended to be exemplary only. A person skilled in the art would appreciate the features of the individual embodiments, and the possible combinations and variations of the components. A person skilled in the art would further appreciate that any of the embodiments could be provided in any combination with the other embodiments disclosed herein. The present examples and embodiments, therefore, are to be considered in all respects as illustrative and not restrictive. Accordingly, while specific embodiments have been illustrated and described, numerous modifications come to mind without significantly departing from the scope defined in the appended claims.

Claims

CLAIMS1 . A method for characterizing a plurality of samples using an analytical technique in a single experimental run, the method comprising: at the beginning of the experimental run, providing a sample of the plurality of samples in each well of a plurality of wells of a multiwell device; for each sample of the plurality of samples: mixing the sample to start or promote the reaction within the well, the sample covering a reaction surface of the well after the reaction; and once the reaction is complete, characterizing the reaction surface of the well, using the analytical technique, wherein the experimental run ends when all the samples of the plurality of samples have been characterized.

2. The method of claim 1 , wherein mixing the sample comprises a solid mixing.

3. The method of claim 1 , wherein mixing the sample comprises a liquid-assisted mixing.

4. The method of claim 1 , wherein mixing the sample comprises a resonant acoustic mixing.

5. The method of claim 1 , wherein mixing the sample comprises a liquid-assisted resonant acoustic mixing.

6. The method of claim 1 , wherein mixing the sample comprises grinding the sample with a mixing media.

7. The method of claim 6, further comprising adding the mixing media to the corresponding well.

8. The method of claim 6 or 7, wherein the mixing media is a metal ring.

9. The method of any one of claims 6 to 8, wherein grinding the sample comprises a liquid-assisted grinding.

10. The method of any one of claims 1 to 9, further comprising heating the sample in the corresponding well.

11. The method of claim 10, wherein the steps of mixing the sample and heating the sample are performed at the same time.

12. The method of claim 10, wherein the steps of mixing the sample and heating the sample are performed according to a predetermined sequence.

13. The method of any one of claims 1 to 12, wherein the reaction surface comprises a bottom portion of the well.

14. The method of any one of claims 1 to 13, wherein the reaction surface comprises a side portion of the well.

15. A multiwell device for assisting a reaction or a filtration process involving a plurality of samples to be characterized using an analytical technique without the need to remove the plurality of samples from the multiwell device, the multiwell device comprising: a stack of plates, comprising: a support plate made from a relatively rigid material containing a plurality of wells in which each well aperture has a flared profile with a chamfered radial exit designed to not obscure or attenuate beams or signals passing through; a substrate or filter plate mechanically connected to the support plate, the substate or filter plate being configured to receive the plurality of samples in regions defined by the plurality of wells of the multiwell device; and at least one additional plate, selected from: a sealing plate to seal the plurality of wells and / or the stack of plates; a substrate or filter plate made from a spectroscopically transparent material and configured to catch material falling thereon;an extension plate comprising extension apertures aligned with the plurality of wells, such that the volume of each well is increased when the extension plate is placed above the plurality of wells; a housing plate sized and configured to receive at least one plate forming the multiwell device; a collection plate comprising a plurality of receptacles, each receptacle being aligned with a corresponding well; a powder transfer plate configured to secure consecutive plates together to form the multiwell device and / or to operate as a sieve; and a top plate extending over one of the support plate containing a plurality of wells in which each well aperture has a flared profile with a chamfered radial entrance designed to not obscure or attenuate beams or signals passing through, the substrate plate or another one of said at least one additional plate, wherein the stack of plates defines the plurality of wells of the multiwell device, each well having a reaction surface and extending through at least a portion of the stack of plates, each well being adapted for receiving a corresponding sample from said plurality of samples on the reaction surface, such that the corresponding sample can be characterized using the analytical technique when the multiwell device is loaded in an analytical instrument.

16. The multiwell device of claim 15, wherein the reaction surface comprises a bottom portion of the well.

17. The multiwell device of claim 15 or 16, wherein the reaction surface comprises a side portion of the well.

18. A filtration multiwell device for characterizing a plurality of samples using an analytical technique, the filtration multiwell device comprising: a support plate made from a relatively rigid material containing a plurality of wells in which each well aperture has a flared profile with a chamferedradial exit designed to not obscure or attenuate beams or signals passing through; a filter plate extending over the sealing plate and configured to receive the plurality of samples in regions defined by a plurality of wells of the filtration multiwell device, the filter plate being made from a spectroscopically transparent material; a first sealing plate extending over the support plate and a second sealing plate extending over the filter plate, such that the filter plate is sandwiched between the first sealing plate and the second sealing plate, the first sealing plate and the sealing plate being adapted to seal the plurality of wells; and a top plate extending over the second sealing plate containing a plurality of wells in which each well aperture has a flared profile with a chamfered radial entrance designed to not obscure or attenuate beams or signals passing through, wherein the support plate, the filter plate, the first sealing plate, the second sealing plate and the top plate collectively define the plurality of wells of the filtration multiwell device, each well having a reaction surface and extending through at least a portion of the filtration multiwell device, each well being adapted for receiving a corresponding sample from said plurality of samples on the reaction surface, such that the corresponding sample can be characterized using the analytical technique when the filtration multiwell device is loaded in an analytical instrument.

19. The filtration multiwell device of claim 18, further comprising a third sealing plate extending over the top plate.

20. The filtration multiwell device of claim 19, further comprising an extension plate extending over the third sealing plate, the extension plate comprising extension apertures aligned with the plurality of wells, such that the volume of each well is increased when the extension plate is placed above the plurality of wells.

21. The filtration multiwell device of any one of claims 18 to 20, wherein the reaction surface comprises a bottom portion of the well.

22. The filtration multiwell device of any one of claims 18 or 21 , wherein the reaction surface comprises a side portion of the well.

23. A reactor multiwell device for characterizing a plurality of samples using an analytical technique, the reactor multiwell device comprising: a support plate made from a relatively rigid material containing a plurality of wells in which each well aperture has a flared profile with a chamfered radial exit designed to not obscure or attenuate beams or signals passing through; a first substrate plate mechanically connected to the support plate, the first substate plate being configured to receive the plurality of samples in regions defined by a plurality of wells of the multiwell device; a sealing plate extending over the first substrate plate; a second substrate plate extending over the sealing plate, such that the sealing plate is sandwiched between the first substrate plate and the second substrate plate; and a top plate extending over the second substrate plate containing a plurality of wells in which each well aperture has a flared profile with a chamfered radial entrance designed to not obscure or attenuate beams or signals passing through, wherein the support plate, the sealing plate, the first substrate plate, the second substrate plate and the top plate collectively define the plurality of wells of the reactor multiwell device, each well having a reaction surface and extending through at least a portion of the reactor multiwell device, each well being adapted for receiving and containing a corresponding sample from said plurality of samples on the reaction surface, such that the corresponding sample can be characterized using the analytical technique when the reactor multiwell device is loaded in an analytical instrument.

24. The reactor multiwell device of claim 23, wherein the reaction surface comprises a bottom portion of the well.

25. The reactor multiwell device of claim 23 or 24, wherein the reaction surface comprises a side portion of the well.

26. A crystallization multiwell device for characterizing a plurality of samples using an analytical technique, the crystallization multiwell device comprising: a support plate made from a relatively rigid material containing a plurality of wells in which each well aperture has a flared profile with a chamfered radial exit designed to not obscure or attenuate beams or signals passing through; a substrate plate mechanically connected to the support plate, the substate plate being configured to receive the plurality of samples in regions defined by a plurality of wells of the multiwell device; a sealing plate extending over the substrate plate; a top plate extending over the substrate plate containing a plurality of wells in which each well aperture has a flared profile with a chamfered radial entrance designed to not obscure or attenuate beams or signals passing through, wherein the support plate, the sealing plate, the substrate plate, and the top plate collectively define the plurality of wells of the reactor multiwell device, each well having a reaction surface and extending through at least a portion of the reactor multiwell device, each well being adapted for receiving a corresponding sample from said plurality of samples on the reaction surface, such that the corresponding sample can be characterized using the analytical technique when the reactor multiwell device is loaded in an analytical instrument.

27. The crystallization multiwell device of claim 26, further comprising a second sealing plate extending over the top plate.

28. The crystallization multiwell device of claim 27, further comprising an extension plate extending over the second sealing plate, the extension plate comprisingextension apertures aligned with the plurality of wells, such that the volume of each well is increased when the extension plate is placed above the plurality of wells.

29. The crystallization multiwell device of any one of claims 26 to 28, wherein the reaction surface comprises a bottom portion of the well.

30. The crystallization multiwell device of any one of claims 26 to 29, wherein the reaction surface comprises a side portion of the well.31 . A micronizing multiwell device for characterizing a plurality of samples using an analytical technique, the micronizing multiwell device comprising: a housing plate; a first sealing plate extending within the housing plate; a collection plate extending over the first sealing plate and comprising a plurality of receptacles, each receptacle being aligned with a corresponding well of a plurality of wells of the micronizing multiwell device; a second sealing plate extending over the collection plate; a support plate made from a relatively rigid material containing a plurality of wells; a substate plate extending over the support plate; and a powder transfer plate configured to secure consecutive plates together to form the multiwell device and / or to operate as a sieve, wherein the plates defines the plurality of wells of the micronizing multiwell device, each well having a reaction surface and extending through at least a portion of the plates, each well being adapted for receiving a corresponding sample from said plurality of samples on the reaction surface, such that the corresponding sample can be characterized using the analytical technique when the micronizing multiwell device is loaded in an analytical instrument.

32. The micronizing multiwell device of claim 31 , wherein the reaction surface comprises a bottom portion of the well.

33. The micronizing multiwell device of claim 31 or 32, wherein the reaction surface comprises a side portion of the well.

34. A micronizing multiwell device for characterizing a plurality of samples using an analytical technique, the micronizing multiwell device comprising: a housing plate; a first sealing plate extending within the housing plate; a collection plate extending over the first sealing plate and comprising a plurality of receptacles, each receptacle being aligned with a corresponding well of a plurality of wells of the micronizing multiwell device; a second sealing plate extending over the collection plate; a powder transfer plate extending over the second filter plate and configured to secure consecutive plates together to form the multiwell device and / or to operate as a filter; a third sealing plate extending over the powder transfer plate; a support plate made from a relatively rigid material containing a plurality of wells; and a substate plate extending over the support plate, wherein the plates define the plurality of wells of the micronizing multiwell device, each well having a reaction surface and extending through at least a portion of the plates, each well being adapted for receiving a corresponding sample from said plurality of samples therein, such that the corresponding sample can be characterized using the analytical technique when the micronizing multiwell device is loaded in an analytical instrument.

35. The micronizing multiwell device of claim 34, wherein the reaction surface comprises a bottom portion of the well.

36. The micronizing multiwell device of claim 34 or 35, wherein the reaction surface comprises a side portion of the well.

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