Systems and methods for increasing convective clearance of undesired particles in a microfluidic device

Patent metadata

Field	Value
Publication number	US-2016158428-A1
Application number	US-201615046152-A
Country	US
Kind code	A1
Filing date	Feb 17, 2016
Priority date	Jan 11, 2013
Publication date	Jun 9, 2016
Grant date	—

Abstract

A microfluidic device for increasing convective clearance of particles from a fluid is provided. In some implementations, described herein the microfluidic device includes multiple layers that each define infusate, blood, and filtrate channels. Each of the channels have a pressure profile. The device can also include one or more pressure control features. The pressure control feature controls a difference between the pressure profiles along a length of the device. For example, the pressure control feature can control the difference between the pressure profile of the filtrate channel and the pressure profile of the blood channel. In some implementations, the pressure control feature controls the pressure difference between two channels such that the difference varies along the length of the channels by less than 50% of the pressure difference between the channels at the channels' inlets.

First claim

What is claimed:

1 . A microfluidic device comprising:
a first layer defining an infusate channel, the infusate channel having a first pressure profile; a second layer defining a blood channel complementary to and in fluidic communication with the infusate channel, the blood channel having a second pressure profile; a third layer defining a filtrate channel complementary to and in fluidic communication with the blood channel, the filtrate channel having a third pressure profile; a first interchannel flow barrier separating the infusate channel and the blood channel; a second interchannel flow barrier separating the filtrate channel and the blood channel; a first controllable flow control device configured to actively control a slope of the third pressure profile along a length of the filtrate channel relative to the slope of the second pressure profile along the length of the blood channel; and a control system configured to modify a state of the first controllable flow control device.

2 . The microfluidic device of claim 1 , wherein the control system is configured to achieve an operational state where the slope of the third pressure profile is greater than the slope of the second pressure profile.

3 . The microfluidic device of claim 1 , wherein the control system is configured to achieve an operational state where the slope of the third pressure profile is less than the slope of the second pressure profile.

4 . The microfluidic device of claim 1 , wherein the control system is configured to achieve an operational state where the slope of the third pressure profile is substantially parallel to the slope of the second pressure profile.

5 . The microfluidic device of claim 1 , wherein the first controllable flow control device is configured such that a pressure difference along a length of the blood channel and the filtrate channel does not vary by more than 50% of an average pressure difference between the blood channel and the filtrate channel.

6 . The microfluidic device of claim 1 , wherein the control system is configured to control the first controllable flow control device to maintain a pressure difference between a pressure of a first fluid flowing through the blood channel and a pressure of a second fluid flowing through the filtrate channel that is below a critical transmembrane pressure.

7 . The microfluidic device of claim 1 , further comprising at least one pressure sensor, wherein the control system is configured to modify the state of the first controllable flow control device responsive to an output of the at least one pressure sensor.

8 . The microfluidic device of claim 1 , wherein the first controllable flow control device is one of a recirculating pump, a proportional valve, a diaphragm chamber, and an outflow pump.

9 . The microfluidic device of claim 1 , further comprising at least two controllable flow control devices configured to actively control the slope of the third pressure profile along the length of the filtrate channel relative to the slope of the second pressure profile along the length of the blood channel.

10 . The microfluidic device of claim 1 , further comprising a second controllable flow control device configured to actively control the slope of the first pressure profile along a length of the infusate channel.

11 . The microfluidic device of claim 10 , wherein the second controllable flow control device is one of a recirculating pump, a proportional valve, a diaphragm chamber, and an influx pump.

12 . The microfluidic device of claim 1 , wherein the blood channel has a height in the range of about 50 μm to about 500 μm, a width in the range of about 50 μm to about 900 μm, and a length in the range of about 3 cm to about 30 cm.

13 . The microfluidic device of claim 1 , wherein the first interchannel flow barrier is a sterility barrier.

14 . A microfluidic device comprising:
a first layer defining a blood channel having an inlet and an outlet and a first pressure profile; a second layer defining a filtrate channel complementary to and in fluidic communication with the filtrate channel, the filtrate channel having a second pressure profile; a first interchannel flow barrier separating the blood channel and the filtrate channel and allowing a portion of a fluid flowing into the inlet of the blood channel to flow through the first interchannel flow barrier and into the filtrate channel; a first controllable flow control device to control a difference between the first pressure profile and the second pressure profile along a length of the blood channel; and a control system configured to modify a state of the first controllable flow control device to set the difference between the first pressure profile and the second pressure profile.

15 . The microfluidic device of claim 14 , wherein setting the difference between the first pressure profile and the second pressure profile comprises modifying the state of the first controllable flow control device such that the difference is less than a critical transmembrane pressure.

16 . The microfluidic device of claim 14 , wherein setting the difference between the first pressure profile and the second pressure profile comprises modifying the state of the first controllable flow control device such that the difference is greater toward the inlet of the blood channel than toward the outlet of the blood channel.

17 . The microfluidic device of claim 14 , wherein setting the difference between the first pressure profile and the second pressure profile comprises modifying the state of the first controllable flow control device such that the difference is greater toward the outlet of the blood channel than toward the inlet of the blood channel.

18 . The microfluidic device of claim 14 , wherein the blood channel has a height in a range of about 50 μm to about 500 μm, a width in the range of about 50 μm to about 900 μm, and a length in the range of about 3 cm to about 30 cm.

19 . The microfluidic device of claim 14 , further comprising a second controllable flow control device to control the difference between the first pressure profile and the second pressure profile along the length of the blood channel.

20 . The microfluidic device of claim 19 , wherein the first and second controllable flow control devices are one of a recirculating pump, a proportional valve, a diaphragm chamber, and an outflow pump.

21 . The microfluidic device of claim 14 , further comprising at least one sensor in the filtrate channel and the blood channel.

22 . A method comprising:
introducing a first fluid into a first inlet of an infusate channel defined in a first layer and having a first pressure profile; introducing blood into a second inlet of a blood channel complementary to and in fluidic communication with the infusate channel, the blood channel having a second pressure profile and defined in a second layer; introducing a second fluid into a third inlet of a filtrate channel complementary to and in fluidic communication with the blood channel, defined in a third layer, and having a third pressure profile; setting, by a control system with a first controllable flow control device, a first slope of the third pressure profile along a length of the filtrate channel relative to the slope of the second pressure profile along the length of the blood channel; and setting, by the control system with the first controllable flow control device, a second slope of the third pressure prof

Assignees

• Draper Lab Charles S
• Johnson & Johnson Innovation LLC

Inventors

• Charest Joseph L
• Nohilly Martin
• Dibiasio Christopher
• Borenstein Jeffrey T
• Laurenzi Mark
• Wilson Jonathan

Classifications

• A61M2202/0413

  Blood · CPC title

• A61M1/1601

  Control or regulation · CPC title

• B01D63/088

  Microfluidic devices comprising semi-permeable flat membranes · CPC title

• B01D61/28

  Apparatus therefor · CPC title

• A61M1/3437

  downstream of the filter, e.g. post-dilution with filtrate · CPC title