# US 2014/0197105 A1 · Systems and methods for increasing convective clearance of undesired particles in a microfluidic device

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- Number: US 2014/0197105 A1
- Document ID: US20140197105A1
- Status: Published application
- Kind: A1
- Application number: 13/739,685
- Filed: 2013-01-11
- Published: 2014-07-17
- Earliest claimed: 2013-01-11
- Assignees: The Charles Stark Draper Laboratory, Inc.
- Inventors: Christopher DiBiasio; Daniel I. Harjes; Joseph L. Charest; Jeffrey T. Borenstein
- Web page: https://patentgrep.com/patent/US20140197105A1

## CPC

- A61M 1/16: with membranes
- A61M 1/34: Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
- A61M 1/3403: {Regulation parameters}
- A61M 1/36: Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation {; Extra-corporeal blood circuits}
- B01D 61/244: {comprising multiple dialysis steps}
- B01L 3/502753: {characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation}
- A61M 2205/0244: Micromachined materials, e.g. made from silicon wafers, microelectromechanical systems [MEMS] or comprising nanotechnology
- A61M 2205/3331: Pressure; Flow
- B01D 63/088: {Microfluidic devices comprising semi-permeable flat membranes}
- B01D 2315/16: Diafiltration
- B01L 2200/0631: Purification arrangements, e.g. solid phase extraction [SPE]
- B01L 2300/0681: Filter
- B01L 2300/0861: Configuration of multiple channels and/or chambers in a single devices
- A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)}
- B01D: SEPARATION (separating solids from solids by wet methods B03B, B03D; by pneumatic jigs or tables B03B; by other dry methods B07; magnetic or electrostatic separation of solid materials from solid materials or fluids, separation by high-voltage electric fields B03C; centrifuges, vortex apparatus B04; presses per se for squeezing-out liquid from liquid-containing material B30B9/02; treatment of water C02F, e.g. softening by ion-exchange C02F1/42; {arrangements of air intake cleaners in gas turbine plants F02C7/05} ; arrangements or mounting of filters in air-conditioning, air-humidification or ventilation F24F13/28)
- B01L: CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE

## Abstract

A microfluidic device for increasing convective clearance of particles from a fluid is provided. A network of first channels can be separated from a network of second channels by a first membrane. The network of first channels can also be separated from a network of third channels by a second membrane. Fluid containing an analyte can be introduced in the network of first channels. Infusate can be introduced into the network of second channels, and waste-collecting fluid can be introduced into the network of third channels. A pressure gradient can be applied in a direction perpendicular to the direction of fluid flow in the network of first channels, such that the analyte is transported from the network of first channels into the network of third channels through the second membrane.

## Claims

### Claim 1

A microfluidic device, comprising:
one or more First Channels defined by first layer of material;
at least one Second Channel complementary to one or more of the First Channels defined by a second layer of material;
a first filtration membrane separating the one or more First Channels from the at least one Second Channel;
at least one Third Channel, defined by a third layer of material, complementary to one or more of the First Channels; and
a second membrane separating the one or more First Channels from the at least one Third Channel, wherein the at least one Second Channel and the at least one Third Channel are configured to allow fluid to flow in a direction perpendicular to a plane of the first layer of material, and the one or more First Channels are configured to receive a net infusion of fluid from the at least one Second Channel and are further configured to provide a net outflow of fluid into the at least one Third Channel.

### Claim 2 (depends on 1)

The microfluidic device of claim 1, further comprising a fluid introduction device configured to flow fluid in the at least one Second Channel in a direction perpendicular to a direction of fluid flow in the one or more First Channels such that fluid flows from the at least one Second Channel into the one or more First Channels and from the one or more First Channels into the at least one Third Channel.

### Claim 3 (depends on 1)

The microfluidic device of claim 1, further comprising at least one structural support within at least one of the one or more First Channels, the at least one Second Channel, or the at least one Third Channel, the structural support configured to limit deformation of the first filtration membrane or the second membrane.

### Claim 4 (depends on 3)

The microfluidic device of claim 3, wherein the at least one structural support comprises a porous mesh including at least one material selected from the group consisting of ceramic, carbon, and polymer.

### Claim 5 (depends on 3)

The microfluidic device of claim 3, wherein the at least one structural support comprises a post or ridge placed within the one or more First Channels, the at least one Second Channel, or the at least one Third Channel.

### Claim 6

(canceled)

### Claim 7 (depends on 1)

The microfluidic device of claim 1, wherein the device is configured such that the volume of a fluid flowing through the one or more First Channels is substantially constant along its length.

### Claim 8 (depends on 1)

The microfluidic device of claim 1, wherein the second membrane has a pore size selected to allow clearance of particles with a molecular weight of no more than about 60 kDa.

### Claim 9

(canceled)

### Claim 10 (depends on 1)

The microfluidic device of claim 1, wherein the microfluidic device is configured such that a hematocrit profile in the one or more First Channels is selectably controllable by an operator of the device when blood is flowed through the one or more First Channels.

### Claim 11 (depends on 1)

The microfluidic device of claim 1, wherein the microfluidic device is configured such that hematocrit is substantially constant throughout the one or more First Channels when blood is transported through the one or more First Channels.

### Claim 12 (depends on 1)

The microfluidic device of claim 1, wherein the one or more First Channels are configured such that fluid flow in the one or more First Channels is substantially laminar.

### Claim 13 (depends on 1)

The microfluidic device of claim 1, wherein the one or more First Channels are configured to maintain wall shear rates in the range of 300-3000 inverse seconds when blood is transported through the one or more First Channels.

### Claim 14 (depends on 1)

The microfluidic device of claim 1, further comprising an anticoagulant coating on at least one inner surface of the one or more First Channels.

### Claim 15

A method for filtering a first liquid containing an analyte to provide a filtered liquid containing less analyte than the first liquid, the method comprising the steps of:
introducing the first liquid into an inlet of one or more First Channels, each First Channel having a height in the range of about 50 microns to about 500 microns, a width in the range of about 50 microns to about 900 microns, and a length in the range of about 3 centimeters to about 20 centimeters;
introducing infusate into at least one Second Channel complementary to the one or more First Channels in a direction perpendicular to the direction of fluid flow in the one or more First Channels, such that at least some of the infusate flows from the at least one Second Channel through a first membrane and into the one or more First Channels;
introducing waste-collecting fluid into at least one Third Channel complementary to the one or more First Channels such that at least some of the analyte of the first liquid is transported through a second membrane into the at least one Third Channel; and
collecting the filtered solution from an outlet of one or more of the First Channels.

### Claim 16 (depends on 15)

The method of claim 15, wherein introducing the first liquid comprises introducing blood.

### Claim 17 (depends on 16)

The method of claim 16, further comprising extracting the blood from a patient and returning filtered blood to the patient.

### Claim 18 (depends on 16)

The method of claim 16, wherein the blood and the infusate are introduced such that hematocrit of the blood is substantially constant throughout the one or more First Channels.

### Claim 19 (depends on 16)

The method of claim 16, wherein the blood is introduced such that a fluid shear rate in the one or more First Channels is within a range of about 300 inverse seconds to about 3000 inverse seconds.

### Claim 20 (depends on 15)

The method of claim 15, wherein the first liquid and the infusate are introduced such that the volume of fluid in each of the one or more First Channels is substantially constant along its length.

### Claim 21 (depends on 15)

The method of claim 15, wherein the first liquid and the infusate are introduced such that fluid flow in the one or more First Channels is substantially laminar.

### Claim 22 (depends on 15)

The method of claim 15, wherein the one or more First Channels include an anticoagulant coating on its walls.

### Claim 23 (depends on 15)

The method of claim 15, wherein the first liquid and the infusate are introduced such that a pressure in the at least one Second Channel is greater than a pressure in the one or more First Channels, and the pressure in the one or more First Channels is greater than a pressure in the at least one Third Channel.

### Claim 24 (depends on 1)

The microfluidic device of claim 1, wherein each First Channel has a height in the range of about 50 microns to about 500 microns, a width in the range of about 50 microns to about 900 microns, and a length in the range of about 3 centimeters to about 20 centimeters