Preparation of Specimen Arrays on an EM Grid
AssigneeThe Scripps Research Institute
InventorsBridget Carragher, Clinton S. Potter, Tilak Jain
Life of this patent
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Abstract
The invention provides methods and compositions for preparation of complex specimen arrays for analysis by electron microscopy. These methods and compositions can permit high throughput screening of samples on single EM grid supports using sample volumes in the nanoliter and picoliter range.
Claims13
A method for preparing an electron microscopy sample on an EM sample grid, comprising:
- dispensing a plurality of discrete specimens onto an EM sample grid in an ordered array of specimen locations, each specimen of the plurality of discrete specimens being placed into an individual specimen location in the array of locations, and each individual specimen location in the array of locations having an area of between about 2000 μm2 to about 70,000 μm2;
- and
- applying a discrete volume of a stain material suitable for contrast enhancement in an electron microscope to each individual specimen location in the array of locations that received a specimen.
A method for preparing an electron microscopy sample on an EM sample grid, comprising:
- dispensing a plurality of discrete specimens onto an EM sample grid in an ordered array of specimen locations, each specimen of the plurality of discrete specimens being placed into an individual specimen location in the array of locations, and each individual specimen location in the array of locations having an area of between about 2000 μm2 to about 70,000 μm2 (for example, each location is a circular spot of between about 50 μm and about 300 μm in diameter);
- applying a discrete volume of a wash solution to each individual specimen location in the array of locations that received a specimen, and removing excess wash solution by contact with a bibulous or porous material at the periphery of each individual specimen location in the array of locations;
- and
- applying a discrete volume of a stain material suitable for contrast enhancement in an electron microscope to each individual specimen location in the array of locations that received a specimen.
An EM specimen grid, comprising:
- a plurality of discrete specimen locations delimited from one another by peripheral regions comprising a bibulous or porous material, each individual specimen location in the array of locations having an area of between about 2000 μm2 to about 70,000 μm2.
A system for dispensing aqueous materials onto an EM sample grid at individual specimen locations in an ordered array of specimen locations, each individual specimen location in the array of locations having an area of between about 2000 μm2 to about 70,000 μm2. The systems comprise:
- a holder for reversibly receiving an EM sample grid;
- a volume drop dispenser configured to dispense fluid from one or more dispensing elements onto each individual specimen location in the array of locations, at least one dispensing element in the volume drop dispenser configured to dispense picoliter volumes;
- a drive mechanism to position the EM sample grid relative to the one or more dispensing elements;
- and
- one or more reservoirs operably linked to the drop dispenser for holding one or more aqueous solutions to be dispensed onto each individual specimen location in the array of locations.
Dependencies are inferred from the claim text.