Abstract:
A microwell including a plurality of MRI-readable indicia. The indicia indicate the identification or location of at least one predefined well or a plurality of wells. The indicia are selected from a mark, figure, number, text, code, barcode, readable texture or indication thereof.

Description:
FIELD OF THE INVENTION 
       [0001]    The present invention generally pertains to microwells with MRI readable indicia and to methods using the same. 
       BACKGROUND 
       [0002]    Microtiter plate or microplate or microwells (herein after: ‘microwell’) is a flat plate with multiple “wells” used as small test tubes. The microplate has become a standard tool in analytical research and clinical diagnostic testing laboratories. A very common usage is in the enzyme-linked immunosorbent assay (ELISA), the basis of most modern medical diagnostic testing in humans and animals. 
         [0003]    A microplate typically has 6, 12, 24, 96, 384 or even 1536 sample wells arranged in a 2:3 rectangular matrix. Some microplates have even been manufactured with 3456 or even 9600 wells, and an “array tape” product has been developed that provides a continuous strip of microplates embossed on a flexible plastic tape. 
         [0004]    Each well of a microplate typically holds somewhere between tens of nanolitres to several millilitres of liquid. They can also be used to store dry powder or as racks to support glass tube inserts. Wells can be either circular or square. For compound storage applications, square wells with close fitting silicone cap-mats are preferred. Microplates can be stored at low temperatures for long periods, may be heated to increase the rate of solvent evaporation from their wells and can even be heat-sealed with foil or clear film. 
         [0005]    Microplates with an embedded layer of filter material were developed in the early 1990s by several companies, and in 1992, the world&#39;s first Solid Phase Extraction (SPE) microplate was launched by Porvair Sciences. This allowed simple column chromatography to be carried out in a microplate footprint for the first time. Today there are microplates for just about every application in life Science research which involves filtration, separation, optical detection, storage, reaction mixing or cell culture. 
         [0006]    The enormous growth in studies of whole live cells has led to an entirely new range of microplate products which are “tissue culture treated” especially for this work. The surfaces of these products are modified using a plasma discharge to make them easier for adherent cells to grow on. 
         [0007]    A number of companies have developed robots to specifically handle SBS microplates. These robots may be liquid handlers which aspirate or dispense liquid samples from and to these plates, or “plate movers” which transport them between instruments, plate stackers which store microplates during these processes, plate hotels for longer term storage or microplate incubators to ensure constant temperature during testing. 
         [0008]    Instrument companies have designed plate readers which can detect specific biological, chemical or physical events in samples stored in these plates. 
         [0009]    It was recently disclosed that MRI is an effective analysis instrument for studying reactions provided in micro scale, namely in microplates, see e.g., Directed evolution of a magnetic resonance imaging contrast agent for noninvasive imaging of dopamine by Mikhail G Shapiro et al.,  Nature Biotechnology,  28, 264-270 (2010). 
         [0010]    A few patents pertain to MRI and microplates. Hence for example, US patent application 2001/0024796 discloses a method of screening a plurality of samples for a selected property, the method comprising: (i) providing an artificially generated physical array, which physical array comprises one or more samples at each of a plurality of spatial locations; (ii) placing the physical array in a magnetic field or applying a magnetic field to the physical array; (iii) performing magnetic resonance imaging spectroscopy (MRI) on the one or more samples of the physical array, thereby identifying the spatial location for each of the one or more samples having one or more MRI detectable chemical shifts, which one or more chemical shifts correspond to the selected property, thereby screening the plurality of samples for the selected property. The application also discloses an apparatus for screening a plurality of samples, the apparatus comprising: (i) a magnetic resonance imaging spectrometer; and, (ii) at least one microwell plate or other artificially generated physical array, wherein during operation of the apparatus the at least one microwell plate or other artificially generated physical array is positioned within a magnetic field produced by the magnetic resonance imaging spectrometer. 
         [0011]    Moreover, various patents discloses means and method for providing indicia in MRI diagnostic. Hence for example, U.S. Pat. No. 6,957,098 discloses a method for locating a catheter, the method comprising: providing a pressure sensitive device attached to a body of a catheter; providing a circuit coupled to the pressure sensitive device in the catheter, generating a magnetic field, the magnetic field inducing and causing the circuit to oscillate; applying a pressure on the pressure sensitive device, the pressure applied on the pressure sensitive device changing an oscillating frequency of the circuit; detecting oscillation of the circuit; and determining location of the catheter based on the oscillation of the circuit. 
         [0012]    None of the above provides a simple solution for precise and simple identification of tested microwell provided online, in situ within an MRI device. Hence MRI-readable microwell indicia fulfills a long felt need. 
       BRIEF SUMMARY 
       [0013]    One aspect of the present invention provides a microwell comprising a plurality of MRI-readable indicia. The indicia indicate the identification or location of at least one predefined well or a plurality of wells. The indicia is selected from a mark, figure, number, text, code, barcode, readable texture or indication thereof. 
         [0014]    Another aspect of the present invention provides a microwell accessory comprising a plurality of MRI-readable indicia. The indicia indicate the identification or location of a predefined well. The indicia is selected from a mark, figure, number, text, code, barcode, readable texture or indication thereof. 
         [0015]    Still another aspect of the present invention provides a method of indicating well identification or location in an MRI-analyzed reaction or medium thereof, comprising providing a microwell with a plurality of MRI-readable indicia and MRI-analyzing the same. The indicia indicate the identification or location of predefined well. The indicia is selected from a mark, figure, number, text, code, barcode, readable texture or indication thereof. 
         [0016]    This Summary is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description. This Summary is neither intended to identify key features or essential features of the claimed subject matter, nor should it be used to limit the scope of the claimed subject matter. Furthermore, the claimed subject matter is not limited to implementations that solve any disadvantage noted in any part of this application. 
         [0017]    The aforementioned and/or other features, aspects, details, utilities, and advantages of the present invention are: set forth in the detailed description which follows and/or illustrated in the accompanying drawings; possibly inferable from the detailed description and/or illustrated in the accompanying drawings; and/or learnable by practice of the present invention. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0018]      FIG. 1  is a schematic illustration of an exemplary embodiment of the present invention; 
           [0019]      FIG. 2  is a schematic illustration of an exemplary embodiment of the present invention; and 
           [0020]      FIG. 3  is a schematic illustration of an exemplary embodiment of the present invention. 
       
    
    
     DETAILED DESCRIPTION 
       [0021]    The following description is provided, alongside all chapters of the present invention, to enable any person skilled in the art to make use of the invention and sets forth the best modes contemplated by the inventor of carrying out this invention. Various modifications, however, will remain apparent to those skilled in the art, since the generic principles of the present invention have been defined specifically to provide microwells with MRI readable indicia and to methods using the same. 
         [0022]    The term ‘Magnetic Resonance Device’ (MRD) specifically applies hereinafter to any Magnetic Resonance Imaging (MRI) device, any Nuclear Magnetic Resonance (NMR) spectroscope, any Electron Spin Resonance (ESR) spectroscope, any Nuclear Quadruple Resonance (NQR) spectroscope or any combination thereof. The MRD hereby disclosed is optionally a portable MRI device, such as the ASPECT Magnet Technologies Ltd commercially available devices, or a commercially available non-portable device. Moreover, the term ‘MRD’ generally refers in this patent to any medical device, at least temporary accommodating an anesthetized animal. 
         [0023]    The term ‘microwell’ refers to microtiter plate or microplate or microwells or microwell array used in laboratory. 
         [0024]    The term ‘microwell accessory’ refers microwell cover, lid, base, stand, or any accessory or appendix known in the art. 
         [0025]    As used herein, the term “plurality” refers in a non-limiting manner to any integer equal or greater than I. 
         [0026]    The term ‘about’ refers herein to a value of ±25% of the defined measure. 
         [0027]    Reference is made to  FIG. 1-3  schematically illustrating (not to scale) various views of a microwell  10  according one embodiment of the invention, comprising a plurality of wells I, and a [plurality of MRI-readable indicia, here for example numbers indication well location in the array  2  and MRI-effective field  3 , a location where the best MRI resolution is apparent. 
         [0028]    According to yet another embodiment of the invention, the indicia is provided not on the microwell, yet on or within the microwell accessory, such as on the microwell base or disposable lid or multiuse cover etc. 
         [0029]    It is well within the scope of the invention wherein indicia are all indicators and material readable by means of MRI, NMR and CT devices, and/or by means of other analysis devices, such as optical instruments. 
         [0030]    According to yet another embodiment of the invention, the indicia is provided within a plurality of all the wells in the microwell. 
         [0031]    According to yet another embodiment of the invention, the indicia is provided remotely or adjacent to a plurality or all the wells in the microwell. 
         [0032]    According to yet another embodiment of the invention, the indicia is temporarily provided, e.g., by providing a plurality of channels were flowing indicia (water or the like) is provided in just before MRI analysis. 
         [0033]    According to yet another embodiment of the invention, the indicia is permanently provided, e.g., by molding the indicia within the microwells. 
         [0034]    According to yet another embodiment of the invention, the indicia is time-resolved, reaction-resolved or composition-resolved. 
         [0035]    Examples of various features/aspects/components/operations have been provided to facilitate understanding of the disclosed embodiments of the present invention. In addition, various preferences have been discussed to facilitate understanding of the disclosed embodiments of the present invention. It is to be understood that all examples and preferences disclosed herein are intended to be non-limiting. 
         [0036]    Although selected embodiments of the present invention have been shown and described individually, it is to be understood that at least aspects of the described embodiments may be combined. 
         [0037]    Although selected embodiments of the present invention have been shown and described, it is to be understood the present invention is not limited to the described embodiments. Instead, it is to be appreciated that changes may be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the claims and the equivalents thereof.