Rapid freeze-quench device and methods of use thereof

Patent metadata

Field	Value
Publication number	US-9513199-B2
Application number	US-201414178310-A
Country	US
Kind code	B2
Filing date	Feb 12, 2014
Priority date	Feb 12, 2013
Publication date	Dec 6, 2016
Grant date	Dec 6, 2016

Abstract

This invention provides mixing, reaction and ejection devices for small volume samples. This invention also provides cooling devices, sample preparation apparatuses and sample preparation methods for studying chemical and biological reactions. The mixing, reaction and ejection devices of this invention allow ejection of small volume liquid samples from a microfluidic channel. Cooling devices of the invention enable serial cooling and collection of samples in an efficient and accurate manner. This invention also provides apparatuses comprising the mixing, reaction and ejection devices and cooling devices. This invention provides methods of using the novel devices and apparatuses.

First claim

What is claimed is:

1. A microfluidic device comprising:
a microfluidic channel comprising a first mixing part and a second reaction part, wherein said channel further comprises a first inlet and a second inlet;
a product outlet, wherein said product outlet is attached to said microfluidic channel; and
a gas compartment surrounding at least a portion of said product outlet such that said gas compartment is coaxial with said product outlet, wherein said gas compartment is attached to a gas inlet channel, and wherein said gas compartment comprises a gas outlet proximal to said product outlet;

wherein upon introduction of a first material from said first inlet and a second material from said second inlet, said first material and said second material are mixed within said first mixing part, and wherein at least a portion of said materials react within said second reaction part and wherein upon ejection of mixed and at least partially reacted materials from said product outlet, a gas from said gas compartment is mixed with said materials thus facilitating ejection of said materials from said product outlet.

2. The device of claim 1 , wherein said first and second inlets are connected to an injection pump.

3. The device of claim 2 , wherein said pump is used to inject said first and second materials through said inlets into said microfluidic channel.

4. The device of claim 2 , wherein said pump controls the flow rate of said first and second materials within said reaction part of said microfluidic channel.

5. The device of claim 1 , wherein the length of said microfluidic channel ranges between 0.5 cm and 4 cm.

6. The device of claim 1 , wherein the height of said channel ranges between 10 μm and 100 μm.

7. The device of claim 1 , wherein the width of said microfluidic channel ranges between 10 μm and 150 μm.

8. The device of claim 1 , wherein said gas compartment is connected to a pressurized gas cylinder.

9. The device of claim 8 , wherein said gas cylinder is used to deliver gas through said gas inlet channel, through said gas compartment and out of said gas outlet.

10. The device of claim 1 , wherein the width of said reaction part of said microfluidic channel is constant.

11. The device of claim 1 , wherein the width of said mixing part of said microfluidic channel varies along the length of said mixing part.

12. The device of claim 1 , wherein said microfluidic channel, said inlets, said gas inlet channel, said gas compartment or a combination thereof are embedded in a first substrate and wherein said first substrate is covered by a second substrate.

13. The device of claim 12 , wherein said first substrate comprises PDMS and said second substrate comprises glass.

14. The device of claim 1 , wherein said microfluidic device comprises a translation element.

15. The device of claim 14 , wherein said translation element translates said microfluidic device along an axis, around an axis or a combination thereof.

16. An apparatus for sample preparation, said apparatus comprising:
a microfluidic device comprising:
a microfluidic channel comprising a first mixing part and a second reaction part, wherein said channel further comprises a first inlet and a second inlet;
a product outlet, wherein said product outlet is attached to said microfluidic channel; and
a gas compartment surrounding at least a portion of said product outlet such that said gas compartment is coaxial with said product outlet, wherein said gas compartment is attached to a gas inlet channel, and wherein said gas compartment comprises a gas outlet proximal to said product outlet;
wherein upon introduction of a first material from said first inlet and a second material from said second inlet, said first material and said second material are mixed within said first mixing part, and wherein at least a portion of said materials react within said second reaction part and wherein upon ejection of mixed and at least partially reacted materials from said product outlet, a gas from said gas compartment is mixed with said materials thus facilitating ejection of said materials from said product outlet;

a cooling device comprising:
a translation element comprising a surface; and
a cooling element;

wherein said translation element contacts said cooling element,
wherein said translation element is cooled by said cooling element, and
wherein said product outlet of said microfluidic device is placed in proximity to said cooling device such that material can be transferred from said microfluidic device onto different areas on said surface of said translation element.

17. The apparatus of claim 16 , wherein said translation element is motorized.

18. The apparatus of claim 17 , wherein said translation element is movable around an axis, along an axis or a combination thereof.

19. The apparatus of claim 16 , wherein the distance between said surface of said translation element and said product outlet, ranges between 2.5 mm and 7.5 mm.

20. The apparatus of claim 16 , wherein said translation element comprises a rigid translation stage.

21. The apparatus of claim 16 , wherein said translation element comprising a belt.

22. The apparatus of claim 16 , wherein said cooling element comprises contacting said translation element with liquid nitrogen.

23. The apparatus of claim 22 , wherein said translation element is a translation stage or a translation belt.

24. The apparatus of claim 23 , wherein said translation stage is conical in shape such that the top of said surface of said translation stage is in the form of a circle, and wherein the bottom conical area of the translation stage which is smaller in diameter from said top of said surface is cooled by liquid nitrogen.

25. The apparatus of claim 16 , wherein said microfluidic device comprises a translation element.

26. The apparatus of claim 25 , wherein said translation element translates said microfluidic device along an axis, around an axis or a combination thereof.

27. A method of preparation of samples for analysis, said method comprising:
a. providing an apparatus for analysis, said apparatus comprising:
a microfluidic device comprising:
a microfluidic channel comprising a first mixing part and a second reaction part, wherein said channel further comprises a first inlet and a second inlet;
a product outlet, wherein said product outlet is attached to said microfluidic channel; and
a gas compartment surrounding at least a portion of said product outlet such that said gas compartment is coaxial with said product outlet, wherein said gas compartment is attached to a gas inlet channel, and wherein said gas compartment comprises a gas outlet proximal to said product outlet;
wherein upon introduction of a first material from said first inlet and a second material from said second inlet, said first material and said second material are mixed within said first mixing part, and wherein at least a portion of said materials react within said second reaction part and wherein upon ejection of mixed and at least partially reacted materials from said product outlet, a gas from said gas compartment is mixed with said materials thus facilitating ejection of said materials from said product outlet; and

a cooling device comprising:
a translation element comprising a surface; and
a cooling element;

wherein said translation element contacts said cooling element,
where

Assignees

• Yeda Res & Dev
• Yeda Res & Dev

Inventors

• Goldfarb Daniella
• Kaufmann Royi

Classifications

• B01L2200/0636

  Focussing flows, e.g. to laminate flows · CPC title

• B01L7/50

  Cryostats · CPC title

• B01F5/0647

  Operations & Transport · mapped topic

• B01L3/5027

  by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip · CPC title

• G01N1/42 Primary

  Low-temperature sample treatment, e.g. cryofixation · CPC title