High throughput screening of crystallization materials

• US 20060196409A1
• Filed: 05/01/2006
• Published: 09/07/2006
• Est. Priority Date: 04/06/2001
• Status: Active Grant

• Current Assignee: California Institute of Technology, Regents of the University of California (University of California)
• Original Assignee: California Institute of Technology, Regents of the University of California (University of California)
• Inventors: Quake, Stephen R., Hansen, Carl L., Berger, James M.
• Granted Patent: US 7,479,186 B2
• Time in Patent Office: Days
• US Class Current: 117/3
• CPC Class Codes: B01D 9/00 Crystallisation crystallisation directly from the vapour phase B01D7/02; making single crystals C30B ; crystallisation as part of the Bayer process also classified in C01F7/14
• CPC Class Codes: B01D 9/0072 Crystallisation in microfluidic devices
• CPC Class Codes: B01D 9/0077 Screening for crystallisation conditions or for crystal forms
• 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 2219/00274 Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
• CPC Class Codes: B01J 2219/00286 Reactor vessels with top and bottom openings
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00389 Feeding through valves
• CPC Class Codes: B01J 2219/00418 using pressure
• CPC Class Codes: B01J 2219/00432 Photolithographic masks
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00756 Compositions, e.g. coatings, crystals, formulations
• CPC Class Codes: B01J 2219/00891 Feeding or evacuation
• CPC Class Codes: B01J 2219/00907 using membranes
• CPC Class Codes: B01J 2219/00952 Sensing operations
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0816 : Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0861 : Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/123 : Flexible; Elastomeric
• CPC Class Codes: B01L 2300/14 : Means for pressure control
• CPC Class Codes: B01L 2300/18 : Means for temperature control
• CPC Class Codes: B01L 2400/0481 : squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0655 : pinch valves
• CPC Class Codes: B01L 2400/0688 : surface tension valves, capillary stop, capillary break
• CPC Class Codes: B01L 3/06 : Crystallising dishes
• CPC Class Codes: B01L 3/5025 : for parallel transport of multiple samples
• CPC Class Codes: B01L 3/50273 : characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502738 : characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 3/502753 : characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• CPC Class Codes: B01L 7/54 : using spatial temperature gradients
• CPC Class Codes: B01L 9/527 : for microfluidic devices, e.g. used for lab-on-a-chip
• CPC Class Codes: B81B 2201/051 : Micromixers, microreactors
• CPC Class Codes: B81B 2201/054 : Microvalves
• CPC Class Codes: B81B 2203/0127 : Diaphragms, i.e. structures separating two media that can control the passage from one medium to another; Membranes, i.e. diaphragms with filtering function
• CPC Class Codes: B81B 2203/0315 : Cavities
• CPC Class Codes: B81C 1/00119 : Arrangement of basic structures like cavities or channels, e.g. suitable for microfluidic systems
• CPC Class Codes: B81C 99/0065 : Process control; Yield prediction
• CPC Class Codes: C30B 29/00 : Single crystals or homogeneous polycrystalline material with defined structure characterised by the material or by their shape
• CPC Class Codes: C30B 29/54 : Organic compounds
• CPC Class Codes: C30B 29/58 : Macromolecular compounds
• CPC Class Codes: C30B 7/14 : the crystallising materials being formed by chemical reactions in the solution
• CPC Class Codes: F04B 43/043 : Micropumps
• CPC Class Codes: F04B 43/14 : having plate-like flexible members
• CPC Class Codes: F16K 2099/0074 : using photolithography, e.g. etching
• CPC Class Codes: F16K 2099/0078 : using moulding or stamping
• CPC Class Codes: F16K 2099/008 : Multi-layer fabrications
• CPC Class Codes: F16K 99/0001 : Microvalves microdevices B81B1/00; manufacture or treatment of devices or systems in or on a substrate B81C1/00; microfluidic structures B01L3/5027; micropumps F04B19/006
• CPC Class Codes: F16K 99/0015 : Diaphragm or membrane valves
• CPC Class Codes: F16K 99/0046 : using magnets
• CPC Class Codes: F16K 99/0051 : using electrostatic means
• CPC Class Codes: F16K 99/0059 : actuated by a pilot fluid
• CPC Class Codes: Y10T 117/10 : Apparatus
• CPC Class Codes: Y10T 117/1004 : with means for measuring, testing, or sensing
• CPC Class Codes: Y10T 117/1008 : with responsive control means
• CPC Class Codes: Y10T 117/1024 : for crystallization from liquid or supercritical state

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

1-18. -18. (canceled)

19. A method for mixing a first reactant and a second reactant comprising:

providing a microfabricated elastomeric block having a chamber therein;

introducing into the chamber a volume of the first reactant; and

introducing a volume of the second reactant into the chamber by entrapping a volume of the second reactant proximate to the chamber and then opening an elastomeric valve positioned between the chamber and the second reactant to allow entry of the second reactant into the chamber.

23. The method of claim 19 wherein the chamber is defined by a junction between a first flow channel that intersects a second flow channel, and wherein the first reactant is flowed through the first flow channel and the second reactant is flowed through the second flow channel.

24. The method of claim 23 wherein an array of chambers is defined by a junction between a first set of flow channels to that intersect a second set of flow channels, and wherein first reactants are flowed through the first flow channels and second reactants are flowed through the second flow channels to create an array of first-reactant-second-reactant conditions.

33. The method recited in claim 19 wherein the first reactant enters the chamber by diffusing into the chamber.

20-22. -22. (canceled)

25-32. -32. (canceled)

34. A method for mixing a first reactant and a second reactant comprising:

providing a microfabricated elastomeric structure having a chamber therein;

introducing the first reactant into the chamber;

introducing a volume of the second reactant into the first reactant in the chamber, wherein the second reactant is introduced into the chamber by entrapping a volume of the second reactant proximate to the chamber, and then opening an elastomeric valve positioned between the chamber and the second reactant to allow entry of the second reactant into the chamber; and

,

obtaining an image of the elastomeric structure.

35. The method recited in claim 34 wherein the second reactant enters the chamber by diffusing into the chamber.

38. The method of claim 34, wherein the inspecting is performed using a microscope.

36. A method for mixing a first reactant and a second reactant comprising:

providing a microfabricated elastomeric structure having a chamber therein;

introducing the first reactant into the chamber and

introducing a volume of the second reactant into the first reactant in the chamber, wherein the second reactant is introduced into the chamber by entrapping a volume of the second reactant proximate to the chamber, and then opening an elastomeric valve positioned between the chamber and the second reactant to allow entry of the second reactant into the chamber; and

,

inspecting the chamber after introducing the volume of the second reactant into the first reactant.

37. The method recited in claim 36 wherein the second reactant enters the chamber by diffusing into the chamber.

39. A system for mixing a first reactant and a second reactant, the system comprising:

a microfabricated elastomeric structure having a chamber therein;

a volume of a first reactant contained within the chamber; and

a volume of a second reactant entrapped proximate to the chamber and separated from the chamber by an elastomeric valve,

wherein, in use, opening of the valve allows mixing of the first reactant and the second reactant.

40. The system of claim 39 wherein the microfabricated elastomeric structure comprises a plurality of chambers.

41. The system of claim 39 wherein the microfabricated elastomeric structure comprises a first elastomeric layer having a first flow channel disposed therein, and a second elastomeric layer, having a second flow channel disposed therein, which flow channels are disposed one above the other and at an angle to one another with a membrane separating the top of one flow channel from the bottom of the other, wherein a valve is formed at the intersection of the first and second flow channels, and wherein at least one flow channel is in fluid communication with the chamber.

42. The system of claim 41 wherein the width-to-depth ratio of at least one channel is 3:

1 and 15;

1 and wherein the width of at least one flow channel is less than 1000 microns.

43. The system of claim 42 wherein the width of at least one flow channel is between 0.2 and 500 microns.