Crystal growth devices and systems, and methods for using same

• US 20050019794A1
• Filed: 04/19/2004
• Published: 01/27/2005
• Est. Priority Date: 04/17/2003
• Status: Active Grant

• Current Assignee: Fluidigm Corporation
• Original Assignee: Fluidigm Corporation
• Inventors: Facer, Geoffrey, Nassef, Hany Ramez, Barco, Joseph W.
• Granted Patent: US 7,279,146 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00355 peristaltic
• CPC Class Codes: B01J 2219/00389 Feeding through valves
• CPC Class Codes: B01J 2219/00396 Membrane valves
• CPC Class Codes: B01J 2219/00398 in multiple arrangements
• CPC Class Codes: B01J 2219/00495 Means for heating or cooling the reaction vessels
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00599 Solution-phase processes
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/00756 Compositions, e.g. coatings, crystals, formulations
• CPC Class Codes: C30B 29/54 Organic compounds
• CPC Class Codes: C30B 29/58 Macromolecular compounds
• CPC Class Codes: C30B 35/002 Crucibles or containers
• CPC Class Codes: C30B 7/00 Single-crystal growth from solutions using solvents which are liquid at normal temperature, e.g. aqueous solutions from molten solvents C30B9/00; by normal or gradient freezing C30B11/00; under a protective fluid C30B27/00
• CPC Class Codes: C40B 40/06 Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 60/08 Integrated apparatus specially adapted for both creating and screening libraries

Abstract

High throughput screening of crystallization of a target material is accomplished by simultaneously introducing a solution of the target material into a plurality of chambers of a microfabricated fluidic device. The microfabricated fluidic device is then manipulated to vary the solution condition in the chambers, thereby simultaneously providing a large number of crystallization environments. Control over changed solution conditions may result from a variety of techniques, including but not limited to metering volumes of crystallizing agent into the chamber by volume exclusion, by entrapment of volumes of crystallizing agent determined by the dimensions of the microfabricated structure, or by cross-channel injection of sample and crystallizing agent into an array of junctions defined by intersecting orthogonal flow channels.

Claims

1. A device for positioning protein crystal within an energy beam comprising:

a chip for holding said crystal therein, said chip being made from an elastomeric block having disposed therein a deflectable membrane;

an adapter plate for connecting said chip to a post, said chip being connected to said adapter plate through one or more posts penetrating into said chip; and

,

a goniometer, wherein said post is connected to said post for positioning said crystal within said beam.

2. The device of claim 1 wherein said adapter plate is movably translatable so as to further position said crystal within an axis perpendicular to said beam.

3. The device of claim 1 wherein said goniometer is rotatable about an axis perpendicular and intersecting said beam, and said chip is rotated about said axis of said beam so as to expose different facets of said crystal to said beam.

4. A method for making a multilayered microfluidic device comprising a molded layer, said method comprising the steps of:

providing a molding substrate;

forming a first mold layer in a pattern; and

,

forming a second mold layer upon portions of said first mold layer;

wherein said pattern has at least two different height dimensions ranging between 1 μ

m and 1000 μ

m;

casting a liquid polymer upon said mold to form said molded layer; and

,

combining said molded layer with a second layer to form said microfluidic device.

5. The method of claim 4 wherein at least one of said portions molds a chamber in said molded layer.

6. The method of claim 4 wherein at least one of said portions molds a recess in said molded layer.

7. The method of claim 4 wherein said mold layer is formed from a photoresist material.

8. The method of claim 4 wherein said pattern comprises a first chamber mold and a second chamber mold, said first chamber mold and said second chamber mold being connected by a recess mold.

9. A microfluidic device made using the method of claim 8 wherein said molded layer comprises a first chamber and a second chamber connected by a recess, said first chamber or said second chamber, or both said first and said second chambers being of a different height dimension than said channel or recess.

10. The microfluidic device of claim 9 further comprising a deflectable membrane deflectable into said channel or recess.

11. A microfluidic device comprising:

a first layer having a first recess formed therein, said recess having a first depth and a second depth and a width dimension between 0.1 μ

m and 1000 μ

m; and

,

a second layer bonded to said first layer.

12. The microfluidic device of claim 11 wherein said second layer further comprises a recess molded therein, said second recess having a width dimension between 0.1 μ

m and 1000 μ

m, wherein a portion of said second recess and a portion of said first recess overlap; and

,

a membrane formed at said overlap and separating said first recess from said second recess to form a deflectable membrane.

13. The microfluidic device of claim 11 wherein at least one layer comprises an elastomeric material.

14. The microfluidic device of claim 11 further comprising a substrate layer wherein said substrate layer imparts rigidity to said microfluidic device.

15. The microfluidic device of claim 12 wherein said elastomeric material comprises polydimethylsiloxane (PDMS).