Patent Application
20080060995
The present disclosure provides a semi-permeable membrane and methods for producing the same.
According to one embodiment, the present invention provides a semi-permeable film or membrane formed from a polymer. The polymer may be hydrophobic or hydrophilic, as desired, in order to impart such qualities to the membrane. According to some embodiments, the membrane may have a thickness of between 200 nm and 150 μm and include a plurality of smooth-surfaced through-holes extending through the membrane.
According to some embodiments, the through-holes may have a diameter of between 20 nm and 2500 nm. Moreover, the through-holes may have a substantially uniform density.
Scanning Electron Microscope (SEM) images of exemplary membranes according to this embodiment are shown in
According to one embodiment, and as described in greater detail below, the membrane may be adjacent to, formed on, attached to, or otherwise associated with a substrate. Accordingly, the membrane may be flexible, chemically dissolvable, or retain various other chemical and physical properties.
At 12, a reservoir holding a suspension fluid is provided. According to one embodiment, the suspension fluid is water. However, other suspension fluids may be used including, for example, chloroform, dichloromethane and heavily halogenated solvents or polymers, water-salt systems such as brine or ammonium chloride, etc, simply ionic liquid such as [EtNH3] [NO3], etc. or binary ionic liquids from mixtures of aluminum (III) chloride and N-alkylpyridinium or 1,3-dialkylimidazolium chloride, etc. Of the above, water, or water-salt systems such as brine or ammonium chloride, etc, simply ionic liquid such as [EtNH3] [NO3], etc. or binary ionic liquids from mixtures of aluminum (III) chloride and N-alkylpyridinium or 1,3-dialkylimidazolium chloride, etc. would be suitable for the preparation of hydrophobic membranes while chloroform, methylene chloride, and other heavily halogenated solvents or polymers would be suitable for preparing hydrophilic membranes.
At 14, a liquid material or a solution of the material is applied to the top of the suspension fluid. According to one embodiment, the material may be applied to the surface of the suspension fluid, for example by pouring, spraying, jetting or other means. Regardless of the method used, the material is applied such that the material is able to spread out and form a thin film on top of the fluid.
Various types of materials may be used depending upon the desired properties of the semi-permeable membrane. According to one embodiment, the material is a hydrophobic polymer. Examples of suitable polymers include, but are not limited to, poly(methyl methacrylate) and its copolymer or block polymer, poly(alkyl acrylate) and its copolymer or block polymer, poly(alkyl methacrylate) and its copolymer or block polymer, poly(acrylamide) and its copolymer or block polymer, poly(N-alkyl acrylamide) and its copolymer or block polymer, poly(N-isopropyl acrylamide) and its copolymer or block polymer, poly(N,N-dialkyl acrylamide) and its copolymer or block polymer, poly(methacrylamide) and its copolymer or block polymer, poly(N-alkyl methacrylamide) and its copolymer or block polymer, poly(N-isopropyl methacrylamide) and its copolymer or block polymer, poly(N,N-dialkyl methacrylamide) and its copolymer or block polymer, poly(ethylene oxide) and its copolymer or block polymer, poly(vinyl chloride) and its copolymer or block polymer, poly(vinyl fluoride) and its copolymer or block polymer, poly(aryl ether) and its copolymer or block polymer, poly(vinyl ether) and its copolymer or block polymer, poly(vinyl acetate) and its copolymer or block polymer, poly(vinyl butyral) and its copolymer or block polymer, poly(vinyl formal) and its copolymer or block polymer, poly(acrylonitrile) and its copolymer or block polymer, poly(methacrylonitrile) and its copolymer or block polymer, poly(siloxane) and its copolymer or block polymer, and poly(styrene) and its copolymer or block polymer, poly(butylene) and its copolymer or block polymer, poly(isobutylene) and its copolymer or block polymer, poly(isoprene) and its copolymer or block polymer, poly(propylene) and its copolymer or block polymer, poly(methylpentene) and its copolymer or block polymer, poly(vinyl alcohol) and its copolymer or block polymer, poly(ethylene glycol) and its copolymer or block polymer. According to one embodiment, the polymer is dissolved in a suitable solvent before it is applied over the suspension fluid. Examples of suitable solvents include, but are not limited to, ethyl acetate, isopropyl alcohol, acetone, ethyl methyl ketone, acetophenone, N-methyl 2-pyrrolidinone, tetrahydrofuran, methylene chloride, anisole, xylene, toluene, chlorobenzene and chloroform, etc. It will be appreciated that the concentration of polymer in the solvent may be varied depending upon the particular materials used and the desired properties of the membrane. However, without wishing to be limited to only these concentrations, polymer concentrations of between about 0.1% and about 15% would be appropriate for certain applications.
At 16, the suspended material is compacted to form a membrane having a plurality of substantially uniformly sized through-holes (or pores). Examples of suitable compaction methods include, but are not limited to, Langmuir-Blodgett trough techniques, the use of pressure fields, contracting rings, and the like. The use of a Longmuir Blodgett technique is described below in the Examples section.
As stated, the membrane includes a plurality of substantially uniformly sized through-holes (or pores). For the purposes of the present invention, the term “substantially uniformly sized pores” is intended to mean that the diameter of the pores in a given membrane may vary by up to 5 times.
According to one embodiment, the presently described method may be employed to produce membranes with pores having a diameter of as small as 250 nm and as large as 2500 nm. Moreover, membranes may be produced having pores smaller than 250 nm and even smaller than 20 nm. Furthermore, unlike pores that are formed by drilling, etching or other similar techniques, the pores that are produced via the presently-described method are smooth edged resulting in a membrane with a smooth surface.
According to one embodiment, the degree of compaction influences both membrane thickness and pore density. Accordingly, it is possible to alter the membrane thickness and pore density by altering the degree of compaction of the suspended material.
At 18, a substrate contacts the suspended membrane such that the membrane is transferred to the substrate. The substrate can take any suitable form including, but not limited to, a microfluidic device which may or may not include one or more fluid chambers or channels, fabric, a lithography substrate, or any other flexible or inflexible surface or material suitable for coating with a semi-porous membrane.
Moreover, the membrane may first be transferred to a web, matrix, carrier, or the like, which may or may not include a binding agent. The web, matrix, carrier, etc. (with or without the binding agent) may then be applied to any desirable surface. Examples of suitable binding agents include, but are not limited to, natural glues, artificial glues and thermo-curable or UV curable epoxy adherent resins, etc. Once coated with the semi-porous membrane, the binding agent may be applied to the desirable surface using any suitable technique including, for example, by laminating.
The dipping method may include, for example, drawing the substrate through the membrane at a given velocity while maintaining a given degree of compaction. As stated above, the prescribed drawing speed and direction can influence the thickness of the membrane. According to some embodiments, drawing speeds ranging from 5 mm/min to 100 mm/min can produce membrane thicknesses of between 150 μm and 200 nm.
According to some embodiments, application of the membrane to the substrate may occur as part of a roll-to-roll process such that sheets of substrate material (such as fabric, films or the like) are coated with the semi-porous membrane. The size of the reservoir, the amount of suspension fluid, the amount of material suspended on the suspension fluid, and the size of the substrate drawn through the suspended layer can be adjusted to produce coated sheets of nearly any desired size.
It may be desirable to introduce a time delay between the time when the polymer solution is added to the suspension material and when the substrate is contacted with the suspended film. The amount of time delay, if any, determines the amount of solvent evaporation and needed thickness of the polymeric thin film formation that can occur before the membrane is transferred onto the substrate. According to some embodiments a time delay of between 0 seconds and 300 seconds may be introduced.
The initial position of the substrate typically dictates the way in which the substrate is coated. For example, a single layer of a sufficiently sticky membrane may be transferred to a substrate simply by contacting the substrate to the membrane. Alternatively, the substrate may be submerged in the reservoir before the polymer material is introduced. In such a case, a single pass of the substrate through the liquid-polymer interface (as the substrate is being drawn out of the reservoir) will result in a single layer of the membrane coating the substrate.
Alternatively, the substrate may be initially positioned above (or otherwise outside of) the reservoir. The substrate would then be passed through the liquid-polymer interface twice, once as the substrate enters the reservoir and once as the substrate is removed from the reservoir. This would produce two stacked layers of membrane material on the surface of the substrate. As a further alternative, the substrate could make multiple passes through the liquid-polymer interface, producing multiple layers of membrane coatings. The substrate could be initially positioned in or out of the reservoir, depending on whether an odd or even number of membrane material coatings is desired.
For a roll-to-roll process, the substrate may be fed into the reservoir through a gasket below the suspension fluid surface or through the top of the suspension fluid surface. Moreover, if the substrate enters the tank through the top of the suspension fluid surface, the substrate could enter through the top surface that is separated from the suspended material by the barrier so that there is no film present where the substrate enters the surface. (See, e.g.
Of course it will be appreciated that the membrane described herein may be formed using a variety of suitable techniques. For example, the membrane of the present invention may be formed by spraying or jetting (such as by inkjet technologies) a PMMA (or other suitable) solution onto a substrate. The thickness and/or concentration of the PMMA solution could be adjusted to alter the thickness, pore size, and density of the membrane, as desired. As non-limiting examples, a 2% PMMA solution could be sprayed onto fabric or over filled chambers to form a coating or chamber cover, respectively. These spraying techniques could be used to apply the membrane onto a single substrate, or could be incorporated into a roll-to-roll (or reel-to-reel) processing technique in order to apply the membrane to multiple substrates or long rolls of substrate.
It will be appreciated that the membranes described in the present disclosure can be used in a myriad number of devices, systems, and applications. Descriptions of several, non-limiting, exemplary applications are below. However, it will be appreciated that the membranes of the present disclosure are not limited to only these applications and that various combinations, alterations, and modifications are possible.
The membranes of the present disclosure could be used as fluid barriers, valves, or filters in various fluidics systems. Examples of suitable fluidics systems include, but are not limited to, MEMS, microinjection mechanisms, and the like.
a. Fluid Barrier
The presently-described membrane can be used as a fluid barrier by allowing the membrane to cover the opening of a fluid chamber. The hydrophobic (or hydrophilic) nature of the membrane in addition to the small pore size would then act to prevent leakage out of the chamber of materials with hydrophilic (or hydrophobic) properties.
To provide additional reliability measures, part or all of the inner or outer surfaces of the fluid chamber could contain a hydrophilic (or hydrophobic) coating, increasing the likelihood that fluid within the chamber would remain in the chamber for as long as desired.
For example, a hydrophobic semi-permeable membrane as presently described may be used as a barrier to keep a material with hydrophilic properties inside of a microchamber in a microinjection device until such time as injection is desired. Likewise, a hydrophilic semi-permeable membrane as presently described may be used as a barrier to keep a material with hydrophobic properties inside of a microchamber in a micro-injection device until such time as injection is desired. Microinjection devices such as that described in co-pending U.S. patent application Ser. No. 11/001,367 typically include an array of addressable drug chambers. Each drug chamber typically includes an ejection mechanism and a microneedle or orifice in fluid communication with the chamber. Upon activation of an ejection mechanism, fluid in the associated chamber is ejected out of the chamber, through the microneedle or orifice, and into the injection recipient. It will be easily understood that in such an application, it is extremely desirable to avoid unintentional or inadvertent leakage or ejection of the fluid out of the chamber, as this could lead to lower or higher dosing than desired, either of which could be harmful to a patient. Accordingly, in order to provide extra protection against inadvertent leakage or ejection, the some portion of the walls of the microchamber could be provided with a hydrophilic coating while the injection orifice or needle could be additionally or alternatively provided with a hydrophobic coating. The discontinuity between the hydrophilic chamber walls and the hydrophobic orifice or needle would then require that additional energy be imparted to the fluid in the drug chamber before ejection could be effected.
b. Valve 10
Alternatively, the membrane of the present disclosure may be situated between two adjacent fluid chambers and may act as a valve for fluid traveling between the two chambers. The valve can be actuated, as desired, by changing the pressure dynamics to encourage movement from one side of the membrane to another. The membrane could act as a fluidic diode, or one-way valve, simply by creating a system where the pressure dynamics can only be altered on one side of the membrane.
Because the membrane has no moving parts, the valve would be unlikely to break and could not get “stuck” (i.e. in an open or closed position). Moreover, because the membrane can be specifically manufactured to have a very small pore size, the valve-size can be scaled down for use with extremely small volumes.
Alternatively, or additionally, the membrane may act as both a chamber cover and a valve. Specifically, the membrane may be placed across the opening of an empty chamber and then fluid forced through the membrane and into the chamber by either a capillary force to extract the fluid after a pre-vacuum treatment or by applying pressure slightly in excess of the hydrophobic repulsion of the membrane. This sterile-filling process may prevent possible contamination during or subsequent to the filling process. Once the pressure is removed, the fluid is constrained to the chamber and will not leak out of the membrane unless force is applied in the opposite direction. Furthermore, other contaminants would be discouraged from passing through the membrane.
c. Filter
As a further alternative, because, as previously stated, the pore size can be controlled by altering the drawing speed and degree of compaction, the membrane of the present invention can also be used as a filter. Accordingly, the size of a membrane's pores can be engineered to prevent passage of undesirable items through the membrane. For example, 250 nm pores could easily filter bacteria, which typically range from about 500 nm to 5000 nm in diameter. Moreover, pores smaller than 20 nm could be engineered by controlling the compaction of the material and drawing speed of the substrate. Pores smaller than 20 nm may be able to filter out viruses (which typically range from about 20-400 nm). Accordingly, such filters could be used to create and/or maintain a sterile environment, to sort biological compounds, or for other applications.
As stated above, the membrane of the present invention can be manufactured in large sheets which can then be either directly applied to a substrate such as fabric (i.e. by drawing the fabric through the liquid-polymer interface of the bath), or, which can be first transferred to a carrier, which can then applied to fabric. Fabric coated with a hydrophobic membrane of the present invention would have the desirable characteristic of preventing water (or other liquids) from traveling through the membrane to the fabric—essentially making the fabric both stainproof and waterproof. Moreover, because the membrane is porous, the fabric would also be “breathable”—allowing air to travel from one side to the other and allowing sweat vapor to escape.
Because of the controllable, substantially uniform, pore size, the membranes of the present invention can be applied to a substrate and used in a lithographic process as a mask in order to expose micron-, sub-micron-, or nanometer-sized sections of the substrate to various lithographic techniques such as patterning, etching, deposition, growth, etc.
An LB trough was filled with water. A mixture of Poly(methyl methacrylate) (PMMA) (2% V/V) in 10 mL ethyl acetate was applied over the water and allowed to partially crosslink. The substrate was formed from a coated silicon wafer. The substrate, which was initially immersed in the water, was drawn through the polymer membrane with a drawing speed of 50 mm/min. and a barrier position creating a 100 mm2 area. The membranes were then imaged using a Scanning Electron Microscope (SEM) to determine pore size and density and membrane thickness. Membrane thickness ranged from 200 to 700 nm and pore size was consistently around 1000 nm (1 μm). Images from a scanning electron microscope of exemplary resultant membranes are shown in
A hydrophobic semi-permeable membrane was formed as described above In Example I. A substrate including a fluid chamber was coated with the membrane such that the membrane covered the opening of the chamber.
While the invention has been described with reference to the exemplary embodiments thereof, those skilled in the art will be able to make various modifications to the described embodiments without departing form the true spirit and scope of the disclosure. Accordingly, the terms and descriptions used herein are set forth by way of illustration only and are not meant as limitations.
