Systems and methods for increasing convective clearance of undesired particles in a microfluidic device
Inventors
Charest, Joseph L. • Nohilly, Martin • DiBiasio, Christopher • Borenstein, Jeffrey T. • Laurenzi, Mark • Wilson, Jonathan
Assignees
Charles Stark Draper Laboratory Inc • Johnson and Johnson Innovation LLC
Publication Number
US-10342909-B2
Publication Date
2019-07-09
Expiration Date
2033-01-11
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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.
Core Innovation
The invention provides a microfluidic device designed to increase convective clearance of particles from fluids such as blood in a dialysis system. This device includes multiple layers defining distinct channels for infusate, blood, and filtrate, each with specific pressure profiles. A key aspect of the invention is the inclusion of pressure control features that regulate the pressure differences between these channels along their lengths to maintain these differences within a controlled variation, specifically less than 50% of the initial pressure difference at the channels' inlets.
The device solves the problem of achieving efficient convective solute clearance in compact dialysis devices while maintaining safe hematocrit levels in the blood channel. Traditional devices often have non-linear fluid to red-blood cell volume profiles and varying transmembrane pressures along their length, causing undesirable hematocrit variations and potential damage to membranes due to pressure spikes. By controlling and parallelizing pressure profiles between channels through pressure control features and complementary channel designs, the invention enables uniform convective clearance across the device length without compromising blood health or device compactness.
Claims Coverage
The patent claims define multiple inventive features centered on a microfluidic device with distinct channel layers, pressure profiles, and pressure control mechanisms to manage transmembrane pressure differences for enhanced convective clearance.
Microfluidic device with pressure control by flow regulation
A device comprising infusate, blood, and filtrate channels defined in separate layers, featuring an interchannel flow barrier allowing fluid flow from infusate to blood channel, equipped with pressure sensors and a pressure control feature including a filtrate fluid circuit controlled by a processor and a recirculation pump to maintain pressure difference variation between blood and filtrate channels within 50% of the initial pressure difference.
Secondary pressure control feature for infusate and blood channels
Incorporation of a second pressure control feature that regulates the pressure difference between infusate and blood channels along the length of the channels to vary by less than 50% of the pressure difference at the upstream end, complementing the primary pressure control.
Non-porous interchannel flow barrier with distributed apertures
Utilization of a non-porous material as the interchannel flow barrier with a plurality of apertures distributed across its face, where aperture diameter ranges between about 50 μm and 300 μm and aperture pitch between about 2 cm and 10 cm.
Pressure control by flow restriction material in filtrate channel
A pressure control feature including a fluid flow restriction material substantially filling the filtrate channel, with variable restrictiveness along the channel length to control pressure profiles.
Pressure control by cross-sectional tapering of filtrate channel
Pressure control achieved through a tapering of the cross-sectional area of the filtrate channel along its length to modulate pressure differences.
Linear or step function pressure profiles
The pressure profiles of the infusate, blood, and filtrate channels can be substantially linear or comprise step functions to achieve desired pressure controls.
Interchannel flow barrier with sealed non-porous portions and intrachannel barriers
An interchannel flow barrier comprising a permeable membrane with multiple sealed, non-porous portions, coupled with intrachannel flow barriers defining zones within the infusate channel, each zone receiving infusate through individual inlets possibly controlled by separate pumps.
Multiple parallel channel arrays and membrane configurations
The device includes multiple infusate, blood, and filtrate channels arranged in parallel across their respective layers with defined channel dimensions and filtration membranes separating channels, aiming at scalable and controlled convective clearance.
Recirculation and filtrate withdrawal pumps for pressure control
Inclusion of recirculation pumps forming filtrate and infusate fluid circuits and pumps configured to draw filtrate fluid out of the filtrate circuit to control flow rates and maintain controlled pressure differences.
Tighter pressure difference control ranges
Pressure differences between blood and infusate channels can be controlled to vary by less than 30%, 15%, or as low as 5% of the upstream pressure difference, enabling more precise pressure profile management.
The claims comprehensively cover a multilayer microfluidic device with complementary infusate, blood, and filtrate channels, employing pressure sensors, recirculation pumps, and structural features such as apertures, tapered channels, and flow restriction materials to control pressure profiles tightly along their lengths. These features collectively maintain controlled and stable transmembrane pressure differences, enhancing convective clearance efficiency while preserving blood integrity.
Stated Advantages
Increased convective clearance in a compact dialysis device without unsafe hematocrit levels in the blood channel.
Maintenance of substantially constant pressure differences along channel lengths to ensure stable membrane performance and full membrane utilization for clearance.
Improved durability of filtration membranes by avoiding high transmembrane pressures that lead to clogging or damage.
Flexible control of pressure profiles enabling tailored clearance rates and hematocrit profiles per clinical requirements.
Parallelized pressure profiles improve convective transport efficiency, reducing the need for increased device size or blood flow rates.
Documented Applications
Use in dialysis and hemofiltration systems for increasing convective transport of solutes, such as urea, uric acid, and creatinine, in blood.
Microfluidic convective clearance of blood with controlled infusion of infusate and removal of filtrate through multilayered microchannel devices.
Applications in blood cleansing by maintaining blood health while enhancing filtration efficiency through stable pressure management in microfluidic devices.
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