Microplates and methods for protein crystallization and biotechnology

{
  "publication_number": "US9855557B2",
  "country": "US",
  "kind": "B2",
  "title": "Microplates and methods for protein crystallization and biotechnology",
  "abstract": "Devices and methods for manual and high-throughput protein crystal growth and growth of other biological and organic crystals. A microplate includes a plurality of cells and a frame that defines the cells in the microplate. In each cell there is at least one well open at top. Each well in a cell may be enclosed at bottom, or it may be open at bottom, in which case the well bottom may be sealed by a separate part, which may be, e.g., a separate film or plate (e.g., of plastic, glass or metal) or a molded part.",
  "claims": [
    "1. A microplate comprising: a frame comprising a substantially planar top surface extending in a first plane, a bottom surface extending in a second plane substantially parallel to the first plane, wherein the top surface and the bottom surface are connected and separated by at least one side surface extending in a third plane normal to the first plane and the second plane, and wherein the frame includes a plurality of cells formed therein, each cell comprising: a first well having a top surface extending in the first plane and a bottom surface extending in a second plane configured to contain between 10 and 200 microliters of stationary fluid; a second well having a top surface extending in the first plane separated from the first well by a predetermined width and configured to contain equal to or less than 10 microliters of stationary fluid; wherein said first well and said second well are separated by a barrier wall extending in a first direction from the bottom surface to the top surface and extending in the first plane, and extending in a second direction along a longitudinal axis and the entire predetermined width between the first well and the second well; wherein said first well and said second well are connected via at least one vapor communication conduit comprising at least one groove formed in the top surface of the barrier wall, wherein the groove is positioned between portions of the top surface of the barrier wall that extend in the first plane, and structured to allow vapor communication between said first well and said second well, and to facilitate the inhibition of liquid transfer between said first well and said second well when at least one cell contains a liquid and when said frame is tilted from a horizontal position to the vertical or is inverted or when said frame is subjected to impulsive accelerations; and wherein the top surface of said barrier wall comprises a center point and two end points, and wherein said at least one vapor communication conduit is positioned in the top surface of barrier wall (i) at a position between the center point and one of the two end points of the top surface of said barrier wall, (ii) at an angle to the longitudinal axis, or (iii) where the conduit follows a non-linear path from the first well to the second well such that there is no line-of-sight path through the path; and wherein when the microplate is held in the horizontal orientation the liquids in the first well and in the second well fill the wells to a level below the position of said at least one vapor communication conduit.",
    "2. The microplate of claim 1, wherein said at least one conduit is located adjacent to one of the two end points of the top surface of said barrier wall.",
    "3. The microplate of claim 1, wherein said at least one conduit is non-linear.",
    "4. The microplate of claim 1, wherein said at least one conduit has a width of between about 0.075 millimeters to about 0.25 millimeters.",
    "5. The microplate of claim 1, further comprising a plurality of conduits structured to allow vapor communication between said first well and said second well, and to facilitate the inhibition of liquid transfer between said first well and said second well when at least one cell contains a liquid and when said frame is tilted from a horizontal position to the vertical or is inverted or when said frame is subjected to impulsive accelerations, wherein each of which of said plurality of conduits is carved into the first top surface of said frame.",
    "6. The microplate of claim 1, further comprising a liquid retention ledge that is connected to and extends around at least a portion of an interior perimeter of one of said first well and said second well at a predetermined distance below the top surface of the frame, and projects outward from the interior perimeter forming an aperture with a diameter that is smaller than a diameter of the interior of said one of said first well and said second well.",
    "7. The microplate of claim 6, wherein said liquid retention ledge is structured to facilitate uniform filling of said one of said first well and said second well with liquid as liquid is added and to facilitate the prevention of the formation of air bubbles therein.",
    "8. The microplate of claim 7, wherein said liquid retention ledge is structured to pin the liquid contact line when liquid is added to said one of said first well and said second well thereby facilitating the prevention of the liquid from rising above the level of the liquid retention ledge during the addition of the liquid.",
    "9. The microplate of claim 8, wherein said liquid retention ledge projects outward at a distance of at least 0.2 millimeters from the interior perimeter of said one of said first well and said second well.",
    "10. The microplate of claim 6, wherein said liquid retention ledge is structured to facilitate the prevention of liquid from flowing out of said one of said first well and said second well when said frame is tilted from a horizontal position or when said frame is subjected to impulsive accelerations.",
    "11. The microplate of claim 10, wherein said liquid retention ledge comprises a rectangular cross-section.",
    "12. The microplate of claim 10, wherein said liquid retention ledge comprises a curved bottom portion, wherein said curved bottom portion of said liquid retention ledge is structured to facilitate the prevention of air bubble trapping during filling of said one of said first well and said second well with liquid.",
    "13. The microplate of claim 12, wherein said liquid retention ledge is structured to form a plurality of apertures.",
    "14. The microplate of claim 13, wherein a first one of said plurality of apertures is formed adjacent to the interior perimeter of said one of said first well and said second well.",
    "15. The microplate of claim 14, wherein a second one of said plurality of apertures is substantially centrally formed in said one of said first well and said second well.",
    "16. The microplate of claim 15, wherein each of said first and said second one of said plurality of apertures is substantially circle-shaped.",
    "17. The microplate of claim 16, wherein a diameter of said second one of said plurality of apertures is larger than the diameter of said first one of said plurality of apertures.",
    "18. The microplate of claim 17, wherein said first one of said plurality of apertures has a diameter of about 150 micrometers.",
    "19. The microplate of claim 6, wherein said one of said first well and said second well including said liquid retention ledge further comprises a bottom portion with rounded corners."
  ],
  "description_excerpt": "The invention pertains to the field of biotechnology. More particularly, the invention pertains to improvements to microplates, including those used for protein crystal growth.\n\nMany fields of bioscience and biotechnology use microplates for screening and other experiments. Microplates generally consist of a large number (e.g., 24, 96, 386, 1536) of identical cells arranged in a regular (usually rectangular) array. Each cell contains one or more wells or reservoirs into which liquids or other samples of interest are dispensed. The microplates are generally made by injection molding plastic. After dispensing samples into the wells, the top of the microplate is often sealed to protect the experiment from the environment. Most microplate designs conform to ANSI standards established by the Society for Biomolecular Sciences (SBS).\n\nA specific application of microplates is in the fields of structural biology and X-ray crystallography, where they are used to grow crystals of proteins, nucleic acids, viruses, and other biomacromolecular complexes, and to explore the solubility of proteins in different solutions. Obtaining crystals of suitable size and quality for X-ray diffraction studies remains an important bottleneck in determining structures of biological macromolecules. Solution conditions (pH, salt type and concentration, protein concentration, concentrations of cryoprotectants and other additives) that yield crystal growth must be identified, and then optimized to yield crystals with adequate diffraction resolution for structure determination.",
  "cpc": [
    "B01L 3/5085",
    "B01L 2200/0678",
    "B01L 2300/0829",
    "B01L 2300/0858",
    "B01L 2300/0893",
    "C07K 1/306",
    "C12M 23/12",
    "C30B 35/002"
  ],
  "ipc": [
    "B01L 3/00",
    "C30B 35/00",
    "C12M 1/32"
  ],
  "assignees": [
    "MiTeGen LLC"
  ],
  "inventors": [
    "Robert E. Thorne",
    "Benjamin Apker",
    "Robert Newman"
  ],
  "filing_date": "2013-03-28",
  "publication_date": "2018-01-02",
  "grant_date": "2018-01-02",
  "priority_date": "2012-03-29",
  "application_number": "US-201314385573-A",
  "family_id": "49261231",
  "cited_by_count": 11,
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}