Methods for screening substances in a microwell array
AssigneeMassachusetts Institute of Technology
InventorsIan Hunter, Colin J.H. Brenan, Tanya S. Kanigan
Life of this patent
Estimating the term…
Abstract
Methods for manufacturing and using an apparatus for manipulating and analyzing a large number of microscopic samples of a liquid or materials, including cells, in liquid suspension. Parallel through-holes are formed in a platen and loaded with a liquid. Loading may be performed in such a way as to create a gradient, with respect to the position of the through-holes, of the concentration of a particular substance or of another quantity. Mixing of the contents of through-holes may be obtained by bringing filled microwell arrays into contact with each other with registration of individual through-holes.
Claims26
A method for loading a plurality of disparate sample containers, the sample containers comprising an integral structure, such that the concentration of a specified substance in each container is characterized by a gradient with respect to position of the container within the structure, the method comprising:
- a. introducing a first liquid into the disparate containers;
- and
- b. contacting the containers with a second liquid, the second liquid containing the specified substance, in such a manner that the degree of diffusion of the specified substance into the disparate containers differs in a controlled manner among the containers.
A method for loading a liquid into a plurality of through-holes of a platen, the platen having a top surface, the top surface having an opening to each through-hole, the method comprising:
- a. forming a droplet of the liquid on the end of a liquid transfer device;
- b. moving the fluid transfer device so as to drag the droplet across the top surface of the platen and over the through-holes to be filled;
- c. dispensing the liquid in such a manner as to keep the droplet from being depleted;
- and
- d. withdrawing the droplet from the surface after the through-holes are filled.
A method for loading a liquid sample into a plurality of through-holes of a platen, the method comprising:
- a. filling a plurality of capillary tubes having dispensing ends, the capillary tubes comprising an array;
- b. disposing each dispensing end in proximity to a distinct through-hole;
- and
- c. transferring liquids to the through-holes of the platen through the capillary tubes.
A method for loading a plurality of sample containers, the sample containers comprising an integral structure, such that the concentration of a specified substance in each container is characterized by a gradient with respect to position of the container within the structure, the method comprising:
- a. creating regions of distinct concentration of the specified substance in a liquid, the liquid having a surface;
- and
- b. transferring into distinct containers the liquid from the distinct regions.
A method for manufacturing a platen having two substantially parallel planar surfaces and a plurality of through-holes disposed substantially perpendicularly to the planar surfaces, the method comprising:
- a. providing a sheet of thermoplastic material;
- b. loading the sheet of thermoplastic material into contact with a surface of a die having a plurality of holes;
- and
- c. bringing a punch having a plurality of protrusions of specified cross-section into contact with the sheet of thermoplastic material in such a manner that the protrusions are in alignment with the holes of the die such that through-holes are cut through the thermoplastic material.
A method for manufacturing a platen having two substantially parallel planar surfaces and a plurality of through-holes disposed substantially perpendicularly to the planar surfaces, the method comprising:
- a. providing a sheet of electrically conducting material;
- b. loading the sheet of conducting material into contact with a surface of a die having a plurality of holes;
- and
- c. bringing an EDM mandrel having a plurality of protrusions of specified cross-section into proximity of the sheet of conducting material in such a manner that the protrusions are in alignment with the holes of the die such that through-holes are cut through the conducting material.
A method for providing a hydrophobic coating to a silicon platen having a first and a second surface, the surfaces being substantially parallel, and a plurality of through-holes substantially perpendicular to the surfaces, the method comprising:
- a. oxidizing the first surface;
- b. cleaning the oxidized first surface;
- c. applying a positive pressure of inert gas to the plurality of through-holes from the direction of the second surface;
- and
- d. exposing the first surface to a silanizing vapor agent.
A method for loading a liquid into a plurality of through-hole platens, each platen having a plurality of through-holes, the method comprising:
- a. stacking at least two platens together in such an adjacent manner that at least one of the plurality of through-holes from each platen is registered with a through-hole of each other adjacent platen so as to form at least one continuous channel;
- and
- b. transferring the liquid into each continuous channel.
A method for mixing liquid in at least two platens, each platen having a plurality of through-holes, the method comprising stacking at least two platens together for a specified time, in such a manner that at least one of the plurality of through-holes from each platen connects with a corresponding through-hole of another platen such that liquid is allowed to diffuse between connecting through-holes.
A microlens array for diffusing light, the microlens array comprising,
- a. a microchannel plate having a plurality of parallel microchannels;
- and
- b. a liquid disposed within substantially each of the plurality of the parallel microchannel.
A method for humidifying a system, the method comprising,
- a. filling a microchannel plate with a liquid having a plurality of parallel microchannels;
- and
- b. placing the filled microchannel plate in vicinity of the system to be humidified.
A method for diffusing light, the method comprising:
- a. entraining a fluid in substantially each of a plurality of parallel microchannels having proximal and distal ends, the microchannels comprising a microchannel plate;
- b. illuminating the proximal end of each of the plurality of parallel microchannels with light;
- and
- c. allowing diffuse light to emanate from the distal ends of the micro channel.
A perforated platen having substantially parallel planar surfaces for manipulating distinct liquid samples, each sample having a volume less than 1 microliter, the platen comprising:
- a. an inner layer of hydrophilic material;
- b. two outer layers of hydrophobic material coupled to opposite sides of the inner layer;
- and
- c. a two-dimensional array of through-holes, at least two holes having distinct volumes, for retaining the distinct liquid samples, the through-holes each having a diameter less than 300 micrometers and traversing the inner layer and the two outer layers in a direction substantially perpendicular to the planar surfaces of the platen.
Dependencies are inferred from the claim text.