FLUID SEPARATION DEVICES, SYSTEMS AND METHODS

• US 20110105982A1
• Filed: 02/04/2009
• Published: 05/05/2011
• Est. Priority Date: 02/04/2008
• Status: Active Grant

• Current Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Original Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Inventors: Cortell, Stanley, Reich, Ilan K., Leonard, Edward F.
• Granted Patent: US 8,496,606 B2
• Time in Patent Office: Days
• US Class Current: 604/6.01
• CPC Class Codes: A61M 1/14 Dialysis systems; Artificial kidneys; Blood oxygenators semi-permeable membranes characterised by the material, manufacturing processes therefor B01D71/00; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
• CPC Class Codes: A61M 1/3482 by filtrating the filtrate using another cross-flow filter, e.g. a membrane filter
• CPC Class Codes: A61M 2206/11 Laminar flow
• CPC Class Codes: A61P 13/12 of the kidneys

Abstract

A membraneless separation device can be applied to a variety of treatments, such as the ultrafiltration of blood for a patient with end stage renal disease. An ultrafiltration device can include a membraneless separation device, which separates an incoming blood flow into a substantially cytoplasmic body-free plasma flow and remaining fraction, and a dialysate-free second stage, which selectively removes excess fluid, toxins and other substances from the plasma flow and returns the processed plasma to the membraneless separation device. A treatment protocol can include ultrafiltering blood of a patient using the ultrafiltration device and performing a secondary treatment on the blood of the patient at a reduced frequency compared to the ultrafiltering. The membraneless separation device can also be applied to treatment, analysis, and/or exchange of plasma from blood, or combined with conventional dialyzers to perform dialysis on a cytoplasmic body-free plasma fraction.

Claims

1. A method for treating chronic renal disease of a patient comprising:

priming a membraneless microfluidic channel and wetting a membrane;

performing an ultrafiltration process, for a duration of at least 4 hours, including;

in a portable device, passing blood at a flow rate into the membraneless microfluidic channel having dimensions such that, at the flow rate, a fraction depleted of cytoplasmic bodies from the blood is generated;

removing a portion of the fraction depleted of cytoplasmic bodies from the membraneless microfluidic channel;

extracting at least water from the removed portion of the fraction depleted of cytoplasmic bodies using the membrane; and

returning the removed portion of the fraction depleted of cytoplasmic bodies, minus some water, back to the membraneless microfluidic channel;

the ultrafiltration rate of the ultrafiltration process resulting in a rate of production of ultrafiltrate of less than 0.4 l/hr;

repeating the performing an ultrafiltration process at least daily, the ultrafiltration process requiring no continuous consumption of exogenous fluid; and

performing, at a frequency that is less than daily, a renal replacement therapy in which blood components are exchanged between blood and a sorbent or a substantial supply of exogenous fluid across a membrane;

the repeating either being done on days in which the performing a renal replacement therapy is done or being skipped on the days in which the performing a renal replacement therapy is done.

2. The method of claim 1, wherein the removing a portion of the fraction depleted of cytoplasmic bodies includes blocking the exit of cytoplasmic bodies from the membraneless microfluidic channel by passing the fraction depleted of cytoplasmic bodies through a wall filter having an array of holes whose sizes are less than 1000 nm, the wall filter forming a part of a wall of the membraneless microfluidic channel.

3. The method of claim 1, wherein the removing a portion of the fraction depleted of cytoplasmic bodies includes blocking the exit of cytoplasmic bodies from the membraneless microfluidic channel by passing the fraction depleted of cytoplasmic bodies through a wall filter having an array of holes whose sizes are between 600 and 1000 nm, the wall filter forming a part of a wall of the membraneless microfluidic channel and forming a continuous unobstructed and smooth surface with the wall of the membraneless microfluidic channel.

4. The method of claim 1, wherein the flow rate is at least 0.5 ml/second and less than 5 ml/sec.

5. The method of claim 1, wherein the ultrafiltration process includes positioning the portable device, including the membraneless microfluidic channel, proximate the patient such that blood volume outside the patient'"'"'s body is minimized by minimizing a volume of blood channels.

6. The method of claim 1, wherein the renal replacement therapy includes at least one of hemo filtration, hemodialysis, and hemodiafiltration.

7. The method of claim 1, wherein the renal replacement therapy includes sorption-based dialysis.

8. The method of claim 1, wherein the renal replacement therapy includes dialysis in which blood and a supply of dialysate of at least 10 L are passed across opposite sides of a membrane at least to clear uremic toxins from the blood.

9. The method of claim 1, wherein the ultrafiltration process includes passing the fraction depleted of cytoplasmic bodies across a sorbent configured to remove at least urea therefrom.

10-37. -37. (canceled)

38. A device for performing ultrafiltration of a patient comprising:

a first stage configured to separate an incoming blood flow into a substantially cytoplasmic body-free plasma flow and a remaining blood fraction;

a second stage, which receives the substantially cytoplasmic body-free plasma flow from said first stage, said second stage being configured to selectively remove excess fluid, toxins and other substances from the plasma flow and return the processed plasma to an inlet of the first stage without consuming a blood-normal solution,

the first stage being configured to return the remaining blood fraction to the patient,

the first stage employing a membraneless separation device that separates plasma from blood by forming layers of flow in at least one microfluidic channel, the layers including a cell-enhanced layer and at least one layer depleted of cytoplasmic bodies, thereby permitting the capture and extraction of the at least one layer; and

a housing containing the first and second stages.

39. The device of claim 38, wherein the at least one microfluidic channel includes multiple microfluidic channels, each being a rectilinear channel with a cross-sectional aspect ratio that is greater than 10.

40. The device of claim 38, further comprising a control module contained in said housing, the control module configured to convey plasma from the at least one microfluidic channel at a rate responsive to a rate of the forming of the at least one layer.

41. The device of claim 38, further comprising a power source contained in said housing, the power source being connected to a controller and a pump that pumps at least one of blood and plasma.

42. The device of claim 38, further comprising at least one valve contained in said housing, the at least one valve being configured to regulate a flow of at least one of the blood and plasma.

43. The device of claim 38, wherein the housing is configured to be worn directly adjacent the patient and the housing has an inlet for receiving blood from the patient, an outlet for returning blood to the patient, and a waste outlet for removing ultrafiltrate.

44. The device of claim 38, wherein each of the at least one microfluidic channel has wall filters with a regular array of holes through which the plasma flows, the holes being sized to prevent the flow of cytoplasmic bodies but to permit blocked cells to be swept away from the wall filter by the flow of blood therepast.

45. The device of claim 44, wherein the holes have sizes between 10 and 800 nm and each wall filter having a surface forming a continuous plane with a wetted wall of a respective one of the at least one microfluidic channel.

46. The device of claim 38, further comprising a control module contained in the housing, the control module including an external input/output interface configured to communicate with blood monitoring devices and receive a set of instructions from a user, the control module being configured to receive signals from at least one sensor configured to detect a property of the blood or plasma of the patient and output an indicator thereof on the external input/output interface.

47. The device of claim 46, wherein the control module includes a memory device for storing information from said at least one sensor.

48. The device of claim 46, wherein the at least one sensor includes at least one of a hematocrit sensor, an electrolyte sensor, a glucose sensor, and a potassium sensor.

49. A method for removing excess fluid from a patient comprising:

removing blood from the patient;

separating, from the blood, a substantially cytoplasmic body-free plasma fraction; and

ultrafiltering the plasma fraction by flowing the plasma fraction through a plurality of hollow fiber membranes in an extracorporeal container using a transmembrane pressure differential in the absence of a dialysate or other liquid medium, wherein the separating includes flowing the blood through a membraneless separation device configured to generate the cytoplasmic body-free plasma fraction by causing the diffusion-based movement of cells into at least one respective layer of the blood flow, thereby forming a cytoplasmic body-depleted layer.

50. The method of claim 49, further comprising recirculating the ultrafiltered plasma fraction to the membraneless separation device such that at least a portion of the ultrafiltered plasma fraction is returned to the patient with the blood.

51. The method of claim 49, wherein the membraneless separation device includes a plurality of microfluidic channels, each configured to sheath the blood flowing therethrough with an extraction fluid flow.

52. The method of claim 49, further comprising returning the blood to the patient.

53. A method for removing platelets from blood, comprising:

passing blood and a sheathing fluid through a microchannel in direct contact;

selecting outlet flows at different parts of the microchannel to select respective fractions of the blood, a first fraction containing cells and platelets, a second fraction containing a higher concentration of platelets than the first fraction;

wherein the second fraction is extracted from the microchannel at a region of higher shear than the first fraction.

54. (canceled)

55. A system for treating chronic renal disease of a patient comprising:

means for priming a membraneless microfluidic channel and wetting a membrane;

means for performing an ultrafiltration process, for a duration of at least 4 hours, including;

means for passing blood at a flow rate into the membraneless microfluidic channel having dimensions such that, at the flow rate, a fraction depleted of cytoplasmic bodies from the blood is generated;

means for removing a portion of the fraction depleted of cytoplasmic bodies from the membraneless microfluidic channel;

means for extracting at least water from the removed portion of the fraction depleted of cytoplasmic bodies using the membrane; and

means for returning the removed portion of the fraction depleted of cytoplasmic bodies, minus some water, back to the membraneless microfluidic channel;

the ultrafiltration rate of the ultrafiltration process resulting in a rate of production of ultrafiltrate of less than 0.4 l/hr;

means for repeating the performing an ultrafiltration process at least daily, the ultrafiltration process requiring no continuous consumption of exogenous fluid; and

means for performing, at a frequency that is less than daily, a renal replacement therapy in which blood components are exchanged between blood and a sorbent or a substantial supply of exogenous fluid across a membrane.

56. The system of claim 55, wherein the means for removing a portion of the fraction depleted of cytoplasmic bodies includes means for blocking the exit of cytoplasmic bodies from the membraneless microfluidic channel by passing the fraction depleted of cytoplasmic bodies through a wall filter having an array of holes whose sizes are less than 1000 nm, the wall filter forming a part of a wall of the membraneless microfluidic channel.

57. The system of claim 55, wherein the means for removing a portion of the fraction depleted of cytoplasmic bodies includes means for blocking the exit of cytoplasmic bodies from the membraneless microfluidic channel by passing the fraction depleted of cytoplasmic bodies through a wall filter having an array of holes whose sizes are between 600 and 1000 nm, the wall filter forming a part of a wall of the membraneless microfluidic channel and forming a continuous unobstructed and smooth surface with a wall of the membraneless microfluidic channel.

58. The system of claim 55, wherein the renal replacement therapy includes at least one of hemo filtration, hemodialysis, and hemodiafiltration.

59. The system of claim 55, wherein the renal replacement therapy includes sorption-based dialysis.

60. The system of claim 55, wherein the ultrafiltration process includes passing the fraction depleted of cytoplasmic bodies across a sorbent configured to remove at least urea therefrom.

61. A system for treating chronic renal disease of a patient comprising:

priming a membraneless microfluidic channel and wetting a membrane;

performing daily, for a duration of at least 4 hours, an ultrafiltration process that includes;

means for passing blood at a blood flow rate into the membraneless microfluidic channel configured such that, at the blood flow rate, a fraction depleted of cytoplasmic bodies from the blood is created, the passing resulting in separate layers of the flow of blood, including a higher shear layer and at least one lower shear layer, the fraction depleted of cytoplasmic bodies coinciding with the at least one higher shear layer; and

means for extracting at least water from the fraction depleted of cytoplasmic bodies resulting from the passing;

means for repeating the ultrafiltration process at least daily, the ultrafiltration process requiring no continuous consumption of exogenous fluid; and

means for repeatedly performing, at a frequency that is less than daily, a renal replacement therapy in which blood toxins are removed either by means of a sorbent or, during a single treatment, by exchanging toxins with a substantial volume of medicament.

62-65. -65. (canceled)

66. A device for exchanging plasma of a patient comprising:

a membraneless channel with opposing walls at least one of which has at least one fluid outlet port, the membraneless channel being configured to extract at least a plasma component from the blood of the patient by causing a fraction of blood that is depleted of cytoplasmic bodies, with the at least a plasma component, to form adjacent the opposing walls;

a pump configured to flow plasma out of the membraneless channel from the at least one fluid outlet port; and

a plasma balance regulator configured to meter fresh plasma or other substituent for infusion into the patient at a rate responsive to a rate of extraction of the plasma component from the membraneless channel.

67. The device of claim 66, wherein:

the membraneless channel has an input end and an output end separated by a length and defining a direction of flow through the channel, a ratio of a channel width to a channel depth of more than 10, the channel depth being no more than 1500 μ

m, both the channel width and the channel depth being perpendicular to the direction of flow, the opposing walls are separated by the depth, the at least one fluid outlet port includes an outlet port on each opposing wall for the plasma, each outlet port having a wall filter, and each wall filter has a surface that is continuous with a respective one of the opposing walls such that cells are swept from the surface by the flow of fluid therepast.

68. The device of claim 67, wherein the wall filters have a pore size no greater than 1000 nm.

69. The device of claim 67, wherein the wall filters have a pore size no greater than 300 nm.

70. The device of claim 67, wherein the channel has a depth of about 700 μ

m.

71. The device of claim 66, wherein the plasma balance regulator is configured to remove water from the plasma that flows out of the membraneless channel and to infuse a resulting dewatered plasma into the patient.

72. The device of claim 71, wherein:

the membraneless channel has an input end and an output end separated by a length and defining a direction of flow through the channel, a ratio of a channel width to a channel depth of more than 10, the channel depth being no more than 1500 μ

m, both the channel width and the channel depth being perpendicular to the direction of flow, the opposing walls are separated by the depth, the at least one fluid outlet port having a wall filter with a surface that is continuous with a respective one of the opposing walls such that cells are swept from the surface by the flow of fluid therepast.

73. The device of claim 72, wherein the wall filter has a pore size no greater than 1000 nm.

74. The device of claim 72, wherein the wall filters have a pore size no greater than 300 nm.

75. The device of claim 72, wherein the plasma balance regulator is configured to convey plasma to membraneless channel, whereby the plasma is infused into the patient by mixing with blood.