CA2518667A1 - Systems and methods of blood-based therapies having a microfluidic membraneless exchange device - Google Patents

Systems and methods of blood-based therapies having a microfluidic membraneless exchange device Download PDF

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Publication number
CA2518667A1
CA2518667A1 CA002518667A CA2518667A CA2518667A1 CA 2518667 A1 CA2518667 A1 CA 2518667A1 CA 002518667 A CA002518667 A CA 002518667A CA 2518667 A CA2518667 A CA 2518667A CA 2518667 A1 CA2518667 A1 CA 2518667A1
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CA
Canada
Prior art keywords
fluid
dialysate
blood
extractor
channel
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Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002518667A
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French (fr)
Other versions
CA2518667C (en
Inventor
Edward F. Leonard
Alan C. West
Nina C. Shapley
Zhongliang Tang
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Columbia University of New York
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The Trustees Of Columbia University In The City Of New York
Edward F. Leonard
Alan C. West
Nina C. Shapley
Zhongliang Tang
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Application filed by The Trustees Of Columbia University In The City Of New York, Edward F. Leonard, Alan C. West, Nina C. Shapley, Zhongliang Tang filed Critical The Trustees Of Columbia University In The City Of New York
Publication of CA2518667A1 publication Critical patent/CA2518667A1/en
Application granted granted Critical
Publication of CA2518667C publication Critical patent/CA2518667C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D11/00—Solvent extraction
    • B01D11/02—Solvent extraction of solids
    • B01D11/0288—Applications, solvents
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D11/00—Solvent extraction
    • B01D11/04—Solvent extraction of solutions which are liquid
    • B01D11/0492—Applications, solvents used
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D11/00—Solvent extraction
    • B01D11/04—Solvent extraction of solutions which are liquid
    • B01D11/0496—Solvent extraction of solutions which are liquid by extraction in microfluidic devices
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2206/00—Characteristics of a physical parameter; associated device therefor
    • A61M2206/10—Flow characteristics
    • A61M2206/11—Laminar flow
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures 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

Abstract

The present invention is directed to devices, systems and methods for removing undesirable materials from a sample fluid by contact with a second fluid. The sample fluid flows as a thin layer adjacent to, or between, concurrently flowing layers of the second fluid, without an intervening membrane. In various embodiments, a secondary separator is used to restrict the removal of desirable substances and effect the removal of undesirable substances from blood. The invention is useful in a variety of situations where a sample fluid is to be purified via a diffusion mechanism against an extractor fluid.
Moreover, the invention may be used for the removal of components from a sample fluid that vary in size. When blood is the sample fluid, for example, this may include the removal of 'small' molecules, 'middle' molecules, macromolecules, macromolecular aggregates, and cells, from the blood sample to the extractor fluid.

Claims (43)

1. A membraneless exchange device for extracting components from a sample fluid, comprising:
first, second and third inlet channels;
first, second and third exit channels; and a microfluidic extraction channel connected to the first, second and third inlet channels and the first, second and third exit channels, wherein laminar flows of a first extractor fluid, the sample fluid, and a second extractor fluid are established inside the extraction channel and wherein sheathing of the sample fluid by the first and second extractor fluids substantially limits contact between the sample fluid and the surfaces of the extraction channel.
2. The device of claim 1, wherein at least 90% of the sample fluid is sheathed by the first and second extractor fluids.
3. The device of claim 2, wherein at least 95% of the sample fluid is sheathed by the first and second extractor fluids.
4. The device of claim 1, wherein at least a portion of the sample fluid exits the device with the first extractor fluid through the first exit channel.
5. The device of claim 1, wherein advective transport of molecules within said extraction channel is substantially nonexistent.
6. The device of claim 1, wherein the composition of the first extractor fluid is substantially the same as the composition of the second extractor fluid.
7. The device of claim 1, wherein the sample fluid flow is between the first and second extractor fluid flows.
8. The device of claim 1, further comprising:
a first diverter formed from a portion of the first exit channel and a portion of the second exit channel; and a second diverter formed from a portion of the second exit channel and a portion of the third exit channel.
9. The device of claim 8, wherein a first interface that is formed between the first extractor fluid flow and the sample fluid flow is aligned with at least a portion of the first diverter, and wherein a second interface that is formed between the second extractor fluid flow and the sample fluid flow is aligned with at least a portion of the second diverter.
10. The device of claim 1, wherein the sample fluid is blood fluid.
11. The device of claim 10, wherein the components extracted from the sample fluid are non-cellular components of the blood fluid.
12. The device of claim 1, wherein a first pump is used for controlling the flow of extractor fluid in the extraction channel and wherein a second pump is used for controlling the flow of sample fluid in the extraction channel.
13. The device of claim 12, wherein the first pump is an injection pump that controls the flow of extractor fluid into the extraction channel and wherein the device further comprises a withdrawal pump that controls the flow of extractor fluid out of the extraction channel.
14. The device of claim 1, wherein a source of extractor fluid is connected to said first inlet channel and wherein a source of sample fluid connected to said second inlet channel.
15. The device of claim 14, wherein the sample fluid is blood fluid and the source of sample fluid is a human being.
16. The device of claim 1, wherein the extraction channel has a height of less than 600 µm.
17. The device of claim 1, wherein the extraction channel has a width-to-height ratio of at least ten.
18. A system for extracting components from a sample fluid, comprising:
a device as defined by claim 1; and a secondary processor that receives the first extractor fluid, the second extractor fluid and at least some of the components of the sample fluid upon exiting the extraction channel.
19. The system of claim 18, wherein said secondary processor is a membrane device.
20. The system of claim 18, wherein said secondary processor is a sorption device.
21. A system for performing hemodialysis, comprising:
a membraneless exchange device comprised of:
first and second dialysate inlet channels;
blood inlet and exit channels;
first and second dialysate exit channels; and a microfluidic dialysis channel connected to the first and second dialysate inlet and outlet channels and the blood inlet and exit channels, wherein laminar flows of a first dialysate fluid, blood fluid, and a second dialysate fluid are established in order inside the dialysis channel, and wherein at least some of the components of the blood fluid exits the device through the first and second dialysate exit channels; and a secondary processor that receives the dialysate fluid and the at least some of the components of the blood fluid exiting the device through the first and second dialysate exit channels.
22. The system of claim 21, wherein the secondary processor filters the dialysate fluid and the at least some of the components of the blood fluid exiting the device through the first and second dialysate exit channels and returns the filtered fluid to the first and second dialysate inlet channels.
23. The system of claim 21, wherein the at least some of the components of the blood fluid are substantially non-cellular components of the blood fluid.
24. The system of claim 21, wherein sheathing of the blood fluid by the first and second dialysate fluids substantially limits contact between the blood fluid and the surfaces of the dialysis channel.
25. The system of claim 21, wherein the secondary processor is a membrane device.
26. The system of claim 21, wherein the secondary processor is a sorption device.
27. The system of claim 21, wherein the composition of the first dialysis fluid is substantially the same as the composition of the second dialysis fluid.
28. The system of claim 21, further comprising:
a first diverter formed from a portion of the first dialysate exit channel and a portion of the blood exit channel; and a second diverter formed from a portion of the blood exit channel and a portion of the second dialysate exit channel.
29. The system of claim 21, further comprising:
a first pump for controlling the flow of dialysate fluid in the dialysis channel;
and a second pump for controlling the flow of blood fluid in the dialysis channel.
30. The system of claim 21, wherein the interface between the first dialysate fluid and the blood fluid is varied by adjusting the velocities of the laminar flows of the first dialysate fluid and the blood fluid.
31. The system of claim 21, wherein the interface between the blood fluid and the second dialysate fluid is varied by adjusting the velocities of the laminar flows of the blood fluid and the second dialysate fluid.
32. The system of claim 21, further comprising a reservoir for storing a viscosity agent, wherein the viscosity agent is be mixed with the first and second dialysate fluid to alter the viscosity of the first and second dialysate fluid.
33. The system of claim 21, further comprising a detector for detecting a presence of an undesired blood component within the dialysate fluid upon exiting the dialysis chamber.
34. The system of claim 33, wherein the detector is comprised of a photo detector.
35. The system of claim 33, wherein a first pump for controlling the flow of dialysate fluid in the dialysis channel is adjusted based on said detected presence of an undesired blood component within said dialysate fluid.
36. The system of claim 21, wherein the velocities of the laminar flows of the first dialysate fluid, the blood fluid and the second dialysate fluid are adjusted based on the detected presence of an undesired blood component within the first and second dialysate fluids.
37. The system of claim 21, wherein the first and second dialysate fluids are comprised of at least one of the following: a hyper osmolar solution, a solution high in glucose content, or a polyelectrolye osmotic agent.
38. A method for extracting components from a sample fluid, comprising:
establishing laminar flows of a first extractor fluid, the sample fluid and a second extractor fluid inside a microfluidic extraction channel, wherein sheathing of the sample fluid by the first and second extractor fluids substantially limits contact between the sample fluid and the surfaces of the extraction channel; and withdrawing the first extractor fluid, the sample fluid and the second extractor fluid from the extraction channel such that at least a portion of the sample fluid is removed together with the first extractor fluid and the second extractor fluid and apart from the remainder of the sample fluid.
39. The method of claim 38, wherein the establishing laminar flows comprises:

providing first, second and third inlet channels; and providing first, second and third exit channels.
40. The method of claim 38, further comprising:
providing the first and second extractor fluids and the at least a portion of the sample fluid to a secondary processor.
41. A method for performing hemodialysis, comprising:
establishing laminar flows of a first dialysate fluid, blood fluid and a second dialysate fluid inside a microfluidic extraction channel;
withdrawing the first dialysate fluid, the blood fluid and the second dialysate fluid from the extraction channel such that at least some of the components of the blood fluid are removed together with the first dialysate fluid and the second dialysate fluid and apart from the remainder of the blood fluid; and providing the first and second dialysate fluids and the at least some of the components of the blood fluid to a secondary processor.
42. The method of claim 41, further comprising:
using the secondary processor to filter the first and second dialysate fluids and the at least some of the components of the blood fluid; and returning the filtered fluid from the secondary processor to the extraction channel.
43. The method of claim 42, wherein sheathing of the blood fluid by the first and second dialysate fluids substantially limits contact between the blood fluid and the surfaces of the dialysis channel.
CA2518667A 2003-03-14 2004-03-15 Systems and methods of blood-based therapies having a microfluidic membraneless exchange device Expired - Fee Related CA2518667C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US45457903P 2003-03-14 2003-03-14
US60/454,579 2003-03-14
PCT/US2004/007966 WO2004082796A2 (en) 2003-03-14 2004-03-15 Systems and methods of blood-based therapies having a microfluidic membraneless exchange device

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CA2518667A1 true CA2518667A1 (en) 2004-09-30
CA2518667C CA2518667C (en) 2011-07-19

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US (4) US20040225249A1 (en)
EP (1) EP1622691B1 (en)
JP (1) JP4489761B2 (en)
AT (1) ATE510605T1 (en)
CA (1) CA2518667C (en)
WO (1) WO2004082796A2 (en)

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