Apparatus for assay, synthesis and storage, and methods of manufacture, use, and manipulation thereof
First Claim
1. A method of making a platen of a desired thickness having a plurality of through-holes, the method comprising:
- a) providing a plurality of plates having upper and lower surfaces, wherein one or both of the upper and lower surfaces of at least some of said plurality of plates has continuous, substantially parallel grooves running the length of said surfaces;
b) bonding the upper surfaces of all but one of said plurality of plates to the lower surfaces of the other plates; and
c) if necessary to achieve the desired thickness, slicing the platen substantially perpendicularly to the through-holes, thereby creating a platen of a desired thickness having a plurality of through-holes.
5 Assignments
0 Petitions
Accused Products
Abstract
The invention features methods of making devices, or “platens”, having a high-density array of through-holes, as well as methods of cleaning and refurbishing the surfaces of the platens. The invention further features methods of making high-density arrays of chemical, biochemical, and biological compounds, having many advantages over conventional, lower-density arrays. The invention includes methods by which many physical, chemical or biological transformations can be implemented in serial or in parallel within each addressable through-hole of the devices. Additionally, the invention includes methods of analyzing the contents of the array, including assaying of physical properties of the samples.
84 Citations
72 Claims
-
1. A method of making a platen of a desired thickness having a plurality of through-holes, the method comprising:
-
a) providing a plurality of plates having upper and lower surfaces, wherein one or both of the upper and lower surfaces of at least some of said plurality of plates has continuous, substantially parallel grooves running the length of said surfaces;
b) bonding the upper surfaces of all but one of said plurality of plates to the lower surfaces of the other plates; and
c) if necessary to achieve the desired thickness, slicing the platen substantially perpendicularly to the through-holes, thereby creating a platen of a desired thickness having a plurality of through-holes. - View Dependent Claims (2, 3)
-
-
4. A device for the immobilization of probes, cells, or solvent, said device comprising a platen having a plurality of through-holes, wherein at least some of said through-holes contain a porous material for the immobilization of probes, cells, or solvent.
-
5. A method of making a platen having opposing hydrophobic surfaces and a plurality of hydrophilic through-holes, the method comprising:
-
(a) coating a plate with a material that reacts with amphiphilic molecules;
(b) forming through-holes; and
(c) treating the plate with a solution or vapor of an amphiphilic molecule to provide a platen having hydrophobic coating on surfaces of the platen but not on the walls of the through-holes. - View Dependent Claims (6, 7)
-
-
8. A method of selectively making a coating on the surfaces of a platen having a plurality of through-holes, the method comprising:
-
(a) selectively coating the surfaces of the platen with a material that reacts with amphiphilic molecules; and
(b) treating the platen with a solution or vapor of an amphiphilic molecule to regenerate the hydrophobic coating.
-
-
9. A device comprising:
a platen having two opposing surfaces and a plurality of through-holes extending between the surfaces, wherein the through-holes have walls, and wherein the surfaces and walls have different chemical properties, so that the walls and surfaces can be independently functionalized.
-
10. A method of making a plastic platen of a desired thickness with through-holes, the method comprising:
-
a) potting a plurality of capillaries in the through-holes of a stack of platens comprising at least two platens having through holes;
b) separating adjacent platens by a distance equal to the desired thickness;
c) injecting a plastic-forming material into the space between the separated platens;
d) forming the plastic; and
e) slicing at the interface between the platens and the plastic to form the chips.
-
-
11. A method of making a plastic platen of a desired thickness with through-holes, the method comprising:
-
a) potting a plurality of fibers or wires in the through-holes of a stack of platens comprising at least two platens having through holes;
b) separating adjacent platens by a distance equal to the desired thickness;
c) injecting a plastic-forming material into the space between the separated platens;
d) forming the plastic;
e) withdrawing the fibers or wires from the plastic to form through-holes; and
f) slicing at the interface between the platens and the plastic to form the chips.
-
-
12. A method of creating a chemical array, the method comprising:
-
a) providing a platen having a plurality of through-holes and two opposing surfaces;
b) applying a mask to one or both surfaces of the platen to block at least some of the through-holes, while leaving other through-holes open;
c) exposing a surface of the platen to a reagent so that the reagent enters at least one of the open through-holes; and
d) repeating steps b) and c) with at least one different mask and at least one different reagent to create a chemical array. - View Dependent Claims (13, 14, 15, 16, 17, 18, 19, 20, 21)
-
-
22. A method of creating a chemical array, the method comprising:
-
a) providing a platen having a plurality of through-holes and two opposing surfaces;
b) applying a mask that has one or more reagents on its surface to one or both surfaces of the platen to transfer the reagent from the mask to at least some of the through-holes; and
c) repeating step b) with at least one different mask and at least one different reagent to create a chemical array.
-
-
23. A method for separating samples within a chemical array in a platen, the method comprising:
-
a) providing a platen having a plurality of through-holes and two opposing surfaces;
b) electrophoretically transporting a charged reagent into at least some of the through-holes by placing the platen into an electrophoresis apparatus containing the reagent and applying an electric field parallel to the through-holes; and
c) repeating step b) with at least one different reagent to create a chemical array.
-
-
24. A method of creating a spatially addressable array, the method comprising:
-
a) providing a platen having a spatially addressable plurality of discrete through-holes each having an inner wall, wherein said platen has opposing hydrophobic surfaces; and
b) covalently or non-covalently immobilizing at least one reagent or probe on the inner walls of at least some of the through-holes or on a bead contained within at least one of the through-holes to form a spatially addressable array. - View Dependent Claims (25, 26, 27)
-
-
28. A method of creating a stochastic array, the method comprising:
-
a) providing a platen having a plurality of through-holes; and
b) applying each of a plurality of reagents to the through-holes in a random or semi-random manner to create a stochastic array. - View Dependent Claims (29, 30, 31)
-
-
32. A method of loading a platen having a plurality of through-holes, where the platen has opposing surfaces, the method comprising:
-
a) dipping the platen into a liquid sample comprising a sample to be loaded into the through-holes, thereby loading at least some of the through-holes with the sample; and
b) passing the platen through a liquid that has an affinity for the surfaces of the platen but that is immiscible with the liquid sample, thereby cleaning the surface of the platen of excess sample mixture.
-
-
33. A method of loading a platen having a plurality of through-holes, where the platen has opposing surfaces, the method comprising:
-
a) dipping the platen into a liquid sample comprising a sample to be loaded into the through-holes, thereby loading at least some of the through-holes with the sample; and
b) contacting the platen with a liquid that has an affinity for the surfaces of the platen but is immiscible with the liquid sample, thereby cleaning the surface of the platen of excess sample mixture.
-
-
34. A method of maintaining the viability of an aerobic organism in a platen having a plurality of through-holes, the method comprising:
-
a) loading the aerobic organism into at least some of the through-holes of the platen, and b) submerging the platen into a gas permeable liquid. - View Dependent Claims (35, 36, 37, 38)
-
-
39. A method of mixing volatile samples with other samples, the method comprising:
-
a) providing a platen having a plurality of through-holes;
b) optionally loading some or all of the through-holes with one or more non-volatile samples;
c) loading at least some of the through-holes of the platen with one or more volatile samples to allow the samples in each through-hole to mix with other samples in the same through-hole; and
d) submerging the platen in a liquid immiscible with the volatile samples, where steps b), c) and d) can be performed in any order. - View Dependent Claims (40, 41, 42)
-
-
43. A method of mixing an array of samples, the method comprising:
-
a) providing a platen having a plurality of through-holes, wherein at least some of the through holes are loaded with a first sample or set of samples;
b) providing a substantially flat surface comprising an array of a second sample or set of samples, wherein the second sample or set of samples on the flat surface can be registered with the sample in the platen;
c) registering the platen with the array of the second sample or set of samples on the flat surface; and
d) contacting the platen with the flat surface, wherein the sample in the platen is aligned with the sample on the flat surface. - View Dependent Claims (44, 45, 46, 47)
-
-
48. A method for transferring a reagent or probe to a receptacle from a specific through-hole of a platen comprising a plurality of through-holes, the method comprising:
-
a) placing the platen over the receptacle; and
b) applying a burst of gas, liquid, solid, or a pin to said specific through-hole to transfer said reagent or probe into the receptacle. - View Dependent Claims (49, 50)
-
-
51. A device for filling or draining through-holes in a platen having a plurality of through-holes, the device comprising:
-
a) a holder adapted to accept the platen;
b) a nozzle having an aperture of a suitable size to inject a sample into a single through-hole in said platen; and
c) a valve that controls a flow of a sample through said nozzle, wherein the holder and nozzle can move with respect to each other. - View Dependent Claims (52, 53, 54, 55, 56, 57)
-
-
58. A method of analyzing the kinetics of one or more reactions occurring in at least one of the through holes of a platen, the method comprising:
-
a) providing a first platen having a plurality of through-holes, wherein the through-holes are loaded with a first sample or set of samples;
b) introducing the platen into a detection device;
c) introducing a second platen having a plurality of through-holes into the detection device, wherein the through holes are loaded with sample or reagent;
d) registering and contacting the platens such that contents of the through-holes of said first platen can mix with contents of corresponding through-holes of said second platen; and
e) detecting a change in a physical property of the contents of at least some of the through-holes over time.
-
-
59. A method of analyzing a physical property of a sample in an array, the method comprising:
-
a) providing a platen having a plurality of through-holes, wherein the through-holes are loaded with a sample;
b) placing the platen between two partially transmitting mirrors;
c) illuminating the samples through one of the mirrors; and
d) detecting optical output from the sample. - View Dependent Claims (60, 61, 62)
-
-
63. A method of measuring sample output from an array, the method comprising:
-
a) providing a platen having a plurality of through-holes, wherein the through-holes are loaded with sample;
b) introducing the sample into an array of capillaries;
c) eluting the samples through the capillaries using pulse pressure, creating a non-continuous flow;
d) spotting the eluting samples onto a surface that is moving relative to the capillaries, wherein the spots are discrete and no mixing of the samples occurs; and
e) analyzing a physical property of the spots.
-
-
64. A method of storing a plurality of samples in an assay-ready, high-density format, the method comprising:
-
a) providing a platen having a plurality of through-holes;
b) loading the through-holes with said samples dissolved in a mixture comprising two solvents, a first solvent having a low vapor pressure and a second solvent having a higher vapor pressure; and
c) evaporating the second solvent to result in a plurality of samples in first solvent. - View Dependent Claims (65)
-
-
66. A method of forming a high throughput assay, the method comprising:
-
a) providing a platen having a plurality of through-holes, wherein at least some of the through-holes contain a sample dissolved in a solvent having a low vapor pressure;
b) cooling the platen to a temperature sufficient to freeze the dissolved sample, c) dipping the platen into a solution comprising a reagent, wherein the temperature of the solution is less than the freezing point of the sample, but greater than the freezing point of the reagent solution, d) removing the platen from the reagent solution, and e) warming the platen to a temperature greater than the freezing point of the sample. - View Dependent Claims (67, 68)
-
- 69. A filtration device comprising first and second platens, each having a plurality of through-holes, and a semi-permeable membrane, wherein the platens are aligned such that the through-holes of the first platen are substantially aligned with the through-holes of the second platen and the membrane is sandwiched in between the two platens.
Specification