Fluid processing device

• US 20060013742A1
• Filed: 07/15/2004
• Published: 01/19/2006
• Est. Priority Date: 07/15/2004
• Status: Active Grant

• Current Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Original Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Inventors: Banerjee, Debjyoti, Bahatt, Dar
• Granted Patent: US 7,378,259 B2
• Time in Patent Office: Days
• US Class Current: 422/100
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0803 Disc shape
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0409 centrifugal forces
• CPC Class Codes: B01L 3/5027 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 B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• 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: Y10T 436/11 Automated chemical analysis
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]

Abstract

A fluid processing device and method of using the device are provided. The fluid processing device can include a substrate with a fluid processing pathway at least partially formed in or on the substrate. The fluid processing pathway can include an input end, at least one output end, a first input opening, a plurality of reaction sites each in fluid communication with the first input opening and arranged between the first input opening and the at least one output end. The fluid processing pathway can include a plurality of second input openings including two or more in fluid communication respectively with each of the reaction sites, the second input openings being arranged with the reaction site disposed between the at least one output end and the second input openings. The fluid processing device can include one or more output openings in fluid communication with one or more of the plurality of reaction sites and arranged at the at least one output end of the fluid processing pathway.

Claims

1. A fluid processing device comprising:

a substrate;

a fluid processing pathway at least partially formed in or on the substrate, the fluid processing pathway comprising;

an input end;

at least one output end;

a first input opening;

a plurality of reaction sites each in fluid communication with the first input opening and arranged between the first input opening and the at least one output end;

a plurality of second input openings including two or more in fluid communication respectively with each of the reaction sites, the second input openings being arranged with the reaction site disposed between the at least one output end and the second input openings; and

one or more output openings in fluid communication with one or more of the plurality of reaction sites and arranged at the at least one output end of the fluid processing pathway.

2. The fluid processing device of claim 1, further comprising at least one valve arranged between at least one of the second input openings and at least one of the reaction sites.

3. The fluid processing device of claim 1, further comprising a plurality of valves, and wherein at least one valve is respectively provided between each of the second input openings and the respective reaction sites.

4. The fluid processing device of claim 1, further comprising a plurality of fluid passageways each providing a respective fluid communication between a respective one of the plurality of second input openings and a respective one of the reaction sites.

5. The fluid processing device of claim 1, further comprising a high surface area support material in the plurality of reaction sites.

6. The fluid processing device of claim 5, wherein each of the plurality of reaction sites includes at least one side wall, and the high surface area support material comprises the at least one side wall.

7. The fluid processing device of claim 5, wherein the high surface area support material comprises at least one of porous glass, a gel, and a hydrogel.

8. The fluid processing device of claim 1, wherein the first input opening and each of the plurality of second input openings are sealed openings.

9. The fluid processing device of claim 1, further comprising a cover layer that at least partially seals the first input opening and the plurality of second input openings.

10. The fluid processing device of claim 1, further comprising one or more valves capable of interrupting fluid communication respectively between the one or more first output opening and one or more of the plurality of reaction sites.

11. The fluid processing device of claim 1, wherein the at least one output end comprises a plurality of output ends and the one or more output opening comprises a plurality of output openings arranged respectively at the plurality of output ends.

12. The fluid processing device of claim 1, wherein the fluid processing device has an axis of rotation, the plurality of reaction sites are arranged radially outward of the first input opening and of the plurality of second input openings, with respect to the axis of rotation, and the one or more output opening is arranged radially outward of at least one of the reaction sites, with respect to the axis of rotation.

36. A method of synthesizing a polynucleotide sequence, comprising:

providing the device of claim 5;

introducing a first nucleotide monomer into at least one of the plurality of reaction sites;

attaching a first protected nucleotide monomer to the high surface area support material;

deprotecting the first protected nucleotide monomer to form a first deprotected monomer;

introducing a wash solution into the reaction site;

removing the wash solution from the reaction site;

attaching a second protected nucleotide monomer to the first deprotected monomer to form a protected nucleotide polymer.

37. The method of claim 36, further comprising:

introducing a wash solution to the reaction site;

removing the wash solution from the reaction site;

introducing a cleaving reagent into the reaction site;

cleaving the protected nucleotide polymer or a derivative thereof from the high surface area support material, to form a cleaved polynucleotide; and

removing the cleaved polynucleotide from the reaction site.

38. The method of claim 36, wherein each of the first and second nucleotide monomers comprises a dimethyltrityl-protected phosphoramidite nucleotide monomer.

39. The method of claim 38, wherein deprotecting comprises contacting the first protected nucleotide monomer with an acid to remove the dimethyltrityl group from the phosphoramidite nucleotide monomer.

13. A fluid processing device comprising:

a substrate;

a fluid processing pathway at least partially formed in or on the substrate, wherein the fluid processing pathway includes;

a first input opening;

a plurality of reaction sites each in fluid communication with the first input opening and each containing a high surface area support material;

a plurality of second input openings, wherein each of the second input openings is in fluid communication with a respective one of the plurality of reaction sites;

at least one output chamber in fluid communication with each of the reaction sites; and

at least one output opening formed in the at least one output chamber.

14. The fluid processing device of claim 13, wherein the plurality of second input openings comprises sets of second input openings wherein each second input opening of each set is in fluid communication with the same respective reaction site.

15. The fluid processing device of claim 13, further comprising a plurality of flow channels each respectively providing a fluid communication between a respective one of the second input openings and a respective one of the plurality of reaction sites.

16. The fluid processing device of claim 13, further comprising a plurality of valves each capable of interrupting fluid communication between a respective one of the plurality of second input openings and a respective one of the plurality of reaction sites.

17. The fluid processing device of claim 13, wherein the at least one output chamber comprises a plurality of output chambers, and each output chamber is in fluid communication with a respective one of the reaction sites.

18. A fluid processing device comprising:

a first input opening;

an input chamber in fluid communication with the first input opening including at least a first fluid-contacting surface;

at least one reaction chamber in fluid communication with the input chamber and including at least a second fluid-contacting surface;

at least one waste chamber in fluid communication with the at least one reaction chamber and including at least a third fluid-contacting surface,

wherein the second fluid-contacting surface exhibits a greater hydrophilicity than the first fluid-contacting surface, and the third fluid-contacting surface exhibits a greater hydrophilicity than the second fluid-contacting surface.

19. The fluid processing device of claim 18, further comprising a first channel providing the fluid communication between the input chamber and the reaction chamber, and a second channel providing the fluid communication between the reaction chamber and the waste chamber.

20. The fluid processing device of claim 18, wherein the reaction chamber has a first volume and the waste chamber has a second volume that is greater than the first volume.

21. The fluid processing device of claim 20, wherein the second volume is at least about ten times greater than the first volume.

22. The fluid processing device of claim 18, further comprising high surface area support material in the reaction chamber.

23. A method of synthesizing a polynucleotide sequence comprising:

providing a fluid processing device comprising a reaction chamber and first and second input openings in fluid communication with the reaction chamber;

introducing a first nucleotide monomer into the second input opening of a fluid processing device;

moving the first nucleotide monomer by capillary action from the second input opening into the reaction chamber;

attaching the first nucleotide monomer to a support disposed in the reaction chamber to form a first supported nucleotide monomer;

introducing a first deprotecting reagent into the first input opening;

moving the first deprotecting reagent by capillary action from the first input opening into the reaction chamber to form a deprotected first nucleotide monomer in the reaction chamber;

introducing a wash reagent into the first input opening;

moving the wash reagent by capillary action from the first input opening into the reaction chamber;

moving the first deprotecting reagent out of the reaction chamber;

introducing a second nucleotide monomer into the second input opening;

moving the second nucleotide monomer by capillary action from the second input opening into the reaction chamber;

introducing a wash reagent into the first input opening;

moving the wash reagent by capillary action from the first input opening into the reaction chamber;

moving the wash reagent out of the reaction chamber; and

contacting the second nucleotide monomer with the deprotected first nucleotide monomer in the reaction chamber to form a second supported nucleotide monomer.

24. The method of claim 23, further comprising:

moving additional nucleotide monomer, deprotecting reagent, and wash reagent, into the reaction chamber to form a polynucleotide sequence.

25. The method of claim 23, further comprising:

moving a cleaving reagent by capillary action into the reaction chamber; and

cleaving the second supported polynucleotide sequence from the support to form a cleaved polynucleotide.

26. The method of claim 25, further comprising removing the cleaved polynucleotide from the reaction chamber.

27. The method of claim 23, wherein each of the first and second nucleotide monomers comprises a dimethyltrityl-protected phosphoramidite nucleotide monomer.

28. A method of synthesizing a polynucleotide sequence comprising:

providing a fluid processing device comprising a reaction chamber and first and second input openings in fluid communication with the reaction chamber;

introducing a first nucleotide monomer into the second input opening of a fluid processing device;

moving the first nucleotide monomer by centripetal force from the second input opening into the reaction chamber;

attaching the first nucleotide monomer to a support disposed in the reaction chamber to form a first supported nucleotide monomer;

introducing a first deprotecting reagent into the first input opening;

moving the first deprotecting reagent by centripetal force from the first input opening into the reaction chamber to form a deprotected first nucleotide monomer in the reaction chamber;

moving the first deprotecting reagent out of the reaction chamber;

introducing a first wash reagent into the first input opening;

moving the first wash reagent by centripetal force from the first input opening into the reaction chamber;

introducing a second nucleotide monomer into the second input opening;

moving the second nucleotide monomer by centripetal force from the second input opening into the reaction chamber;

introducing a second wash reagent into the first input opening;

moving the second wash reagent by centripetal force from the first input opening into the reaction chamber;

moving the wash reagent out of the reaction chamber; and

contacting the second nucleotide monomer with the deprotected first nucleotide monomer in the reaction chamber to form a second supported nucleotide monomer.

29. The method of claim 28, wherein the step of moving the first deprotecting reagent out of the reaction chamber occurs after the step of introducing the first wash reagent into the first input opening.

30. The method of claim 28, wherein the step of moving the first deprotecting reagent out of the reaction chamber occurs before the step of introducing the first wash reagent into the first input opening.

31. The method of claim 28, wherein the first and second wash reagents are the same.

32. The method of claim 28, further comprising:

moving additional nucleotide monomer, deprotecting reagent, and wash reagent, into the reaction chamber to form a polynucleotide sequence.

33. The method of claim 28, further comprising:

moving a cleaving reagent by centripetal force into the reaction chamber; and

cleaving the second supported polynucleotide sequence from the support to form a cleaved polynucleotide.

34. The method of claim 33, further comprising removing the cleaved polynucleotide from the reaction chamber.

35. The method of claim 28, wherein each of the first and second nucleotide monomers comprises a dimethyltrityl-protected phosphoramidite nucleotide monomer.