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Microfluidic devices, particularly filtration devices comprising polymeric membranes, and method for their manufacture and use

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Microfluidic devices, particularly filtration devices comprising polymeric membranes, and method for their manufacture and use


The present disclosure describes devices useful for microscale fluid purification, separation, and synthesis. Such devices generally comprise a fluid membrane that separates two or more fluids flowing through plural microchannels operatively associated with the membrane. Often, the membrane is a semipermeable membrane, such as might be used with a filtration device, such as a dialyzer. Devices of the present invention can be combined with other microscale devices to make systems. For example, the devices may be coupled with one or more microchemical microfactories, one or more micromixers, one or more microheaters, etc. Examples of devices made according to the present invention included an oxygenator, a dialyzer, microheat exchangers, etc.

Browse recent The State Of Oregon Acting By And Through The State Board Of Higher Education On Behalf Of patents - ,
Inventors: Goran Jovanovic, Sundar V. Atre, Brian Kevin Paul, John Simonsen, Vincent Thomas Remcho, Chih-Hung Chang
USPTO Applicaton #: #20120292246 - Class: 2103216 (USPTO) - 11/22/12 - Class 210 
Liquid Purification Or Separation > Casing Divided By Membrane Into Sections Having Inlet(s) And/or Outlet(s)

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The Patent Description & Claims data below is from USPTO Patent Application 20120292246, Microfluidic devices, particularly filtration devices comprising polymeric membranes, and method for their manufacture and use.

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CROSS REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No. 13/292,903, filed Nov. 9, 2011, which is a continuation of U.S. patent application Ser. No. 13/068,037, filed Apr. 29, 2011, which is a continuation of U.S. patent application Ser. No. 11/243,937, filed Oct. 4, 2005, which claims the benefit of the earlier filing date of U.S. Provisional Application No. 60/616,877, filed on Oct. 6, 2004. The entire disclosures of these prior applications are incorporated herein by reference.

FIELD

The present disclosure concerns microchannel devices having polymer membranes operatively associated therewith, such as purification devices having membranes for filtering fluids, one example being a dialyzer.

BACKGROUND

There are a number of important systems that require fluid purification, particularly liquid purification. Community water systems, for example, obtain water from local sources, such as lakes and rivers, but such water sources often contain impurities, and also may contain bacteria and other microbiological organisms, that can cause disease. Consequently, water from surface sources must be purified before it can be consumed. Water treatment plants typically clean water by taking it through the following processes: (1) aeration; (2) coagulation; (3) sedimentation; (4) filtration; and (5) disinfection. Portable water purification systems would benefit the production of potable water in areas where there are few if any water treatment plants.

Fluid oxygenators also provide an important example of fluid purification. Oxygenator is the main element of the heart-lung machine, which takes over the work of the lungs by adding oxygen to and removing carbon dioxide from the blood. Inside the oxygenator, blood is channelled along capillary membranes. The inner lumen of the fibres is streamed with oxygen or oxygen enriched air. Oxygen diffuses through the microporous membrane into the blood, while carbon dioxide diffuses out of the blood into the gas stream and is thereby removed. Most oxygenators also include a heat exchanger to maintain the correct temperature of the patient\'s blood. The oxygenated blood is channelled back to the patient.

Another important example of liquid purification is dialysis. The chemical composition of blood must be controlled to perform its essential functions of bringing nutrients and oxygen to the cells of the body, and carrying waste materials away from those cells. Blood contains particles of many different sizes and types, including cells, proteins, dissolved ions, and organic waste products. Some of these particles, including proteins such as hemoglobin, are essential for the body to function properly. Others, such as urea, a waste product from protein metabolism, must be removed from the blood. Otherwise, they accumulate and interfere with normal metabolic processes. Still other particles, including many of the simple ions dissolved in the blood, are required by the body in certain concentrations that must be tightly regulated, especially when the intake of these chemicals varies.

The kidneys are largely responsible for maintaining the chemistry of the blood by removing harmful particles and regulating the blood\'s ionic concentrations, while keeping the essential particles. Kidneys act like dialysis units for blood, making use of different particle sizes and specially-maintained concentration gradients. Blood passes through membrane-lined tubules of the kidney, analogous to the dialysis tubes used in dialysis units. Particles that can pass through the membrane pass out of the tubules by diffusion, thus separating the particles that remain in the blood from those that will be removed from the blood and excreted.

Kidneys can effectively maintain the body\'s chemistry as long as at least ten percent of their functional units are working. Damage to the kidneys that causes the functional capacity to drop below this level may cause fatal illness unless an artificial system performs the work of the kidneys. Without artificial kidney dialysis, toxic wastes build up in the blood and tissues, and cannot be filtered out by the ailing kidneys. This condition is known as uremia, which means literally “urine in the blood.” Tens of thousands of people currently require kidney dialysis, and the number is growing. Kidney dialysis is intrusive, expensive, and complicated. Patients suffer from current treatment protocols due to extensive side effects. Home dialysis is much preferable to the current practice of having patients treated at dialysis centers. Improved technology is needed, however, to make home dialysis feasible and affordable for patients.

Conventional dialysis units are configured as hollow fibers. The membranes are manufactured using spinning technology and generally are about 35μ thick. The membrane is highly porous with the exception of the inner ˜1μ, which actually performs the separation, retaining blood cells but allowing small molecules to diffuse therethrough. These known dialyzers use membranes typically made of cellulose acetate, cuprophan or polysulfone. Blood is pumped through these fibers, and then back into the patient. The membrane has a molecular weight cut-off that allows most solutes in the blood to pass out of the tubing but retains the proteins and cells. Thus, artificial kidney dialysis uses the same chemical principles that are used naturally in the kidneys to maintain the chemical composition of the blood. Diffusion across semipermeable membranes, polarity, and concentration gradients are central to the dialysis process for both natural and artificial kidneys.

SUMMARY

The present invention is directed to microscale fluid purification, separation, and synthesis devices. Generally, such devices comprise a fluid membrane that separates two or more fluids flowing through plural microchannels operatively associated with the membrane. The fluids can both be liquids, gases, or a liquid and a gas, such as may be used for gas absorption into a liquid. Often, the membrane is a semipermeable membrane, such as might be used with a filtration device, such as a dialyzer.

Devices of the present invention can be combined with other devices to make systems. For example, the devices may be coupled with: one or more microchemical microfactories, such as nanofactories useful for making, amongst other materials, dendrimers; one or more micromixers, such as a micromixer comprising posts positioned to impinge fluid flowing to the microchannels or a micromixer comprising regions of hydrophobic surface and hydrophilic surface; one or more microheaters; etc.

One example of a device made according to the present invention is an oxygenator. For this embodiment, the fluid is a gas, namely oxygen. For oxygenating blood, the liquid component is blood.

Microheat exchangers also can be made using the method described herein.

Particular materials had to be developed for use with certain embodiments of the device disclosed herein. For example, a new composite material was made comprising nanocrystalline cellulose filler and a polysulfone polymeric material. The composite can comprise any suitable amount of nanocrystalline cellulose filler, with likely amounts ranging from greater than zero weight percent nanocrystalline filler to about 10 percent filler, and more likely from about 1 percent to about 5 percent nanocrystalline filler. A dialyzer comprising the composite membrane also is disclosed. One embodiment of the dialyzer comprised a dialyzer membrane comprising nanocrystalline cellulose filler and a polysulfone polymeric material, and a microchannel fluidic device fluidly associated with the membrane to provide a blood flow and a dialysate flow adjacent the membrane.

In order to make the nanocrystalline cellulose-polymer composite, a new method was devised for making an organic dispersion of nanocrystalline cellulose. The method comprised first forming an aqueous dispersion of nanocrystalline cellulose. A mixture was then formed comprising the aqueous dispersion and an organic liquid having a boiling point higher than water. The water was then selectively removed to form a second mixture comprising the nanocrystalline cellulose and the organic liquid. Water can be selectively removed by a process similar to distillation, such as by heating the composite mixture to a temperature sufficient to remove the water but not the organic liquid, reducing the pressure sufficient to allow selective water removal, or both. A person of ordinary skill in the art will realize that a number of organic liquids can be used to practice this method. Solely by way of example, and without limitation, the organic liquid may be dimethylformamide, n-methylpyrollidone, tetrahydrofuran, or combinations thereof.

The nanocrystalline cellulose may be prepared from a suitable source, such as a material selected from the group consisting of wood, cotton, Tunicin, Cladophora sp., Valonia, bacteria, chitin, potato starch, and combinations thereof. The nanocrystalline cellulose also may be surface modified to make it more compatible with the polymeric material. The surface modified cellulose may be surface modified by a physical process, such as flame or corona discharge oxidation, or by a chemical process using a material selected, without limitation, from the group consisting of silyl, trimethyl silyl, epoxy, isocyanate, acetate, maleate, sulfate, phosphate, an ester/sulfate mix, anhydrides, and combinations thereof.

BRIEF DESCRIPTION OF THE DRAWINGS

The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.

FIGS. 1A-1C provide AFM images of cellulose nanocrystals, with the top image at 400 nm scale, middle image, a measurement showing a typical length of 191 nm, and the bottom image showing the lowest observed height of 3.7 nm.

FIGS. 2A and 2B schematically illustrates flow mal-distributions that occur on a dialysate side of a conventional fiber-type dialyzer.

FIG. 3 illustrates one embodiment of a microscale dialyzer according to the present invention.

FIGS. 4A-4D are schematic diagrams illustrating one embodiment of a microchannel array having a filter membrane integrally associated therewith.

FIG. 5 is a plan view of one embodiment of a MECS dialyzer according to the present invention.

FIG. 6 is a plan view of the blood flow side and dialysate flow side of one embodiment of a dialyzer according to the present invention.

FIG. 7 is a schematic drawing illustrating a multi-layered dialyzer unit comprising multiple microchannel defining plates and integrally associated polymeric membranes.

FIGS. 8A-8D illustrate plural different diffusion channel design configurations.

FIGS. 9A-9E provide typical dimensions used to make the plates illustrated in FIG. 8.

FIG. 10 is a schematic diagram illustrating one embodiment of an overall dialzyer system according to the present disclosure.

FIG. 11 is a schematic diagram of test device assembled to test microchannel-based fluid filtration.

FIG. 12 is a schematic exploded view of a reactor developed to demonstrate operation of a dialyzer as disclosed herein.

FIG. 13 illustrates different uses for MECS and micrototal analysis systems (OAS).

FIG. 14A is a schematic, cross sectional diagram illustrating an ultrasonic packaging technique before ultrasonically welding with the energy directors protruding above the PDMS layer.

FIG. 14B is a schematic, cross sectional diagram illustrating the result of ultrasonic welding with the energy directors melted down, bonding the top and bottom PC films, compressing the PDMS layer and sealing the microchannels.

FIG. 15 is a photomicrograph illustrating that with appropriate welding time and pressure the energy directors form strong bonds and the PDMS compresses to create a conformal seal against the polycarbonate top and bottom.

FIG. 16 is a diagram of (a) a “nanofractory” producing the generalized structure of a dendrimer as (b) a branched architecture and (c) a 3-D space-filling model.

FIG. 17 is a schematic perspective diagram of one embodiment of an interdigital micromixer.

FIGS. 18A-18B are micrographs of (A) 75 μm thick laser-machined polyimide (200×) and (B) 15 μm thick micromolded PDMS (500×) membranes with 5-8 μm pores on 100 μm spacing.

FIG. 19 is a schematic diagram of an exemplary analytical micromixer with a NSOM (Near-field optical microscopy) ear optical fiber probe.

FIGS. 20A and 20B illustrate one approach to fabricating a “nanofractory”: (a) an in-line fractal design for compact production of dendrimers (geometry based on the work of Pence) and b) a close up of one of the vertices in the fractal device with integrated micromixer, heater and separator.

FIGS. 21A-21B illustrate an alternative modular approach to nanofractory development.

FIG. 22 illustrates using mechanical valves for dendron extraction.

FIGS. 23A-23B are photomicrographs illustrating monolithic sorbent materials produced in PDMS microchannels with sufficient anchoring to yield a useful device for separations.

FIGS. 24A-24C are SEM images of a polymer made using the embodiments of the device described herein.

FIG. 25 is a schematic plan view of a gas-liquid contactor membrane.

FIG. 26 is a schematic drawing illustrating the basic components of a heat exchanging system.

FIG. 27 is a schematic drawing illustrating one embodiment of a method for making a contactor membrane by micromolding techniques.

FIGS. 28-30B illustrate the results obtained by micromolding contactors.



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stats Patent Info
Application #
US 20120292246 A1
Publish Date
11/22/2012
Document #
13560721
File Date
07/27/2012
USPTO Class
2103216
Other USPTO Classes
International Class
01D63/00
Drawings
32



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