BILAYER 2D MATERIAL LAMINATES FOR HIGHLY SELECTIVE AND ULTRA-HIGH THROUGHPUT FILTRATION
1. A 2D material bilayer membrane, comprising:
- a first membrane layer;
an interlinking layer of interlinking molecules disposed on the first membrane layer; and
a second membrane layer disposed on the interlinking layer, where the interlinking molecules electrostatically or covalently interlink the second membrane layer and first membrane layer.
Various examples are provided for highly selective and ultra-high throughput filtration using bilayer two-dimensional (2D) material laminates and highly absorptive medium of 2D material laminates or solution dispersions. In one example, a 2D material bilayer membrane includes a first membrane layer; an interlinking layer of interlinking molecules disposed on the first membrane layer; and a second membrane layer disposed on the interlinking layer. The interlinking molecules electrostatically or covalently interlink the second membrane layer and first membrane layer.
- 1. A 2D material bilayer membrane, comprising:
a first membrane layer; an interlinking layer of interlinking molecules disposed on the first membrane layer; and a second membrane layer disposed on the interlinking layer, where the interlinking molecules electrostatically or covalently interlink the second membrane layer and first membrane layer.
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
- 15. A 2D material bilayer membrane structure, comprising:
a first channel layer comprising a first fluid channel; a 2D material bilayer membrane disposed on the first channel layer over the first fluid channel; and a second channel layer comprising a second fluid channel, the second channel layer disposed on the 2D material bilayer membrane opposite the first channel layer with the second fluid channel aligned with the first channel layer.
- View Dependent Claims (16, 17, 18, 19, 20)
This application claims priority to, and the benefit of, co-pending U.S. provisional application entitled “Bilayer 2D Material Laminates for Highly Selective and Ultra-High Throughput Filtration” having Ser. No. 62/657,086, filed Apr. 13, 2018, which is hereby incorporated by reference in its entirety.
The human body has multiple methods to clear toxins and metabolic products from the bloodstream. Patients with end-stage liver and kidney disease as well as acute organ failure are unable to maintain this necessary clearance and require blood-purification techniques or organ transplant. Due to the limited availability of suitable organ donors and the health of potential recipients, end stage renal disease (ESRD) patients receive regular hemodialysis (HD) treatments in the United States. A smaller number receive artificial liver support therapy for detoxification and liver failure. These blood purification techniques place an extremely high financial burden on the medical system with sometimes questionable efficacy.
Many aspects of the present disclosure can be better understood with reference to the following drawings. The components in the drawings are not necessarily to scale, emphasis instead being placed upon clearly illustrating the principles of the present disclosure. Moreover, in the drawings, like reference numerals designate corresponding parts throughout the several views.
Disclosed herein are various examples related to highly selective and ultra-high throughput filtration using bilayer two-dimensional (2D) material laminates and highly absorptive medium of 2D material laminates or solution dispersions. Reference will now be made in detail to the description of the embodiments as illustrated in the drawings, wherein like reference numbers indicate like parts throughout the several views.
Development of a high throughput and selective membrane technology and a highly absorptive medium with a small volume can help alleviate the high financial burdens of dialysis on patients. A high throughput membrane enables fabrication of a membrane module substantially smaller than the existing technology leading to significant reduction in extracorporeal blood volume. In a typical dialysis session, a person losses 150 ml of blood. Given that a dialysis patient is treated three times a week, the existing technology results in loss of 400-500 ml of blood per week. This is the blood that leaves the patient body to the pipes and membrane module, and is not recovered. Some dialysis patients suffer from anemia. A compact microchannel dialysis cartridge with only several ml of blood volume can alleviate this issue. Such a compact membrane cartridge can be installed on patient'"'"'s body (e.g. forearm) such that only the dialysate fluid connections need to be connected to a machine. Such a breakthrough can alleviate bleeding concerns associated with access to blood vessels in home-based dialysis. Currently, home-based dialysis accounts for only a very small fraction of total dialysis patients.
Current dialyzers utilize hollow-fiber membranes that have remained relatively unchanged for decades. While significant effort has been made to introduce a portable or wearable artificial kidney (WAK), the existing designs utilize conventional but miniaturized HD components, which necessitates extended use and requires qualified patients. The fundamental challenge is that despite many years of system engineering, operation principle and transport characteristics of the membranes utilized in these systems have remained the same. To address patients'"'"' safety concerns and enhance affordability in US and throughout the world, innovative membrane improvements to facilitate toxin removal at low operating flow rates are required. Lower flow rates would enable new vascular access options, to reduce the risk of exsanguination.
Like HD, liver support systems have also been slow to change, utilizing similar dialyzer approaches in combination with often dated adsorption technologies such as activated charcoal and anion exchange columns. Patients receiving artificial liver support receive a fundamentally similar dialysis treatment, but with the goal of removing albumin-bound and lipophilic toxins. This clearance is primarily accomplished through albumin dialysis and/or use of an adsorption column. In both cases, toxin clearance is transport-limited by either the dialyzer membrane or entrance into the adsorptive matrix.
Nano-engineered 2D material laminates and dispersions have the potential to radically improve and change hemodialysis and liver support systems. 2D materials bilayers are the thinnest possible molecular sieve and have tunable physical and surface chemical properties to allow selective clearance of small and middleweight toxins. Additionally, nanoscale spaced 2D materials sheets offer the maximal surface area of any material matrix per unit volume enabling unparalleled adsorptive properties, with extremely high permeability. Preparation and characterization of a 2D material (e.g., graphene oxide (GO)) membrane is presented in “Proton selective ionic graphene-based membrane for high concentration direct methanol fuel cells” by Paneri et al. (Journal of Membrane Science 467 (May 2014) 217-225), which is hereby incorporated by reference in its entirety. These properties would dramatically improve the flexibility to design medical devices that improve survival and quality of life, while reducing cost.
An example of the 2D material (GO) is an atomically-thin functionalized derivative of graphene, comprising a carbon backbone with several oxygen-containing groups (e.g., epoxy, hydroxyl, carboxyl, carbonyl) on the basal plane and edges.
Through a comprehensive study, it has been shown that i) the laminate thickness, ii) nanoplatelets size, iii) surface defects and iv) the inter-layer spacing vastly impact the GO laminates permeability and selectivity. See “Impact of synthesis conditions on physicochemical and transport characteristics of graphene oxide laminates” by Paneri et al. (CARBON 86 (January 2015) 245-255), which is hereby incorporated by reference in its entirety. In the application of GO for reduction of undesirable methanol permeation through a proton exchange membrane (PEM), an order of magnitude better performance was achieved compared to prior studies when the synthesis process of the GO platelets was precisely controlled. Other benefits of GO membranes in dialysis have also been confirmed. In a fundamentally different approach than disclosed here, a composite membrane was made by adding up to 2% GO into a polymer matrix. The addition of the GO into the polymer matrix increased the membrane mean pore size from 32 nm to 76 nm, which increased its permeability. However, the membrane exhibited an increase in biocompatibility: reduced protein adsorption, suppressed platelet adhesion, and lower complement activation.
Here, GO bilayers with a precise control on the interlayer spacing can be produced through layer-by-layer (L-b-L) assembly of GO platelets 103 on a porous polymer support in a highly scalable process.
In terms of material cost, the disclosed configuration can be very economical. Mass production of graphene has improved in recent years due to the large number of potential graphene-based applications. Production of graphene has increased from 15 tons in 2010 to 120 tons in 2014, with the price of graphene being estimated at $1.50/gr. Depending on the number of GO layers, 100s of square meters of a typical polymer support membrane 206 can be covered with a bilayer structure using 1 gr of GO. Therefore, the cost of graphene does not contribute to the overall cost of the membrane, and the cost is dominated by a set of batch chemical processes. The cost of these chemical processes is not substantially different than those used in the fabrication of existing dialysis and ultrafiltration membranes.
In a preliminary test, a molecular assembly of GO nanoplatelets 103 on a polyacrylonitrile (PAN) support membrane 206 was prepared. After hydrolyzing the optimized PAN membrane 206, the L-b-L assembly was conducted to build the GO laminate. Poly(allylamine hydrochloride) (PAH) was used as the interlinking molecule 203. For testing, a 0.2 mM solution of Ibuprofen was supplied to a diffusion cell and the permeated solution was collected and analyzed. For the purpose of comparison, a GE Osmonics membrane was also tested in the same setup. The results were compared with literature data on other membranes and plotted in
The use of nanoengineered 2D laminates and dispersions for the clearance of water-soluble and albumin-bound toxins offers two-fold advantages. First, these materials reduce the needed membrane area by at least an order of magnitude compared to the state-of-the-art, based on thicknesses <10 nm and an increased permeability. In addition, nanospaced 2D laminates offer a theoretical limit on accessible surface area within a fixed volume that is likely to exceed conventional materials by orders of magnitude.
Development and optimization of membranes can include alteration of the physical “pore” size and the surface chemistry.
Referring now to
Using the interlinking molecules, the interlayer spacing can be varied from about 1 nm to about 10 nm and can impact the performance of the membrane. This can be accomplished using PAH and/or poly(dimethyldiallylammonium chloride) (PDDAC) with different molecular weights. PAH can be chemically derived from poly(allylamine phosphate) (PAP), which can be synthesized by solution polymerization of allylamine phosphate (AP) using 2,2′-azo-bis-2-amidinopropane dihydrochloride (AAP.2HCl) as the initiator. Following its synthesis, the PAP can be reacted with concentrated hydrochloric acid to obtain the PAH. Furthermore, smaller covalent linkers such as multivalent metal ions, 1,3,5-benzenetricarbonyl trichloride, and diamine monomers may be utilized. These are non-limiting examples, many other molecules and polymer chains can be used.
The size of GO nanoplatelets can be measured using the Langmuir-Blodgett method and subsequently imaged using a Scanning Electron Microscope (SEM) (e.g., FEI Nova NanoSEM 430) in conjunction with image analysis software (e.g., ImageJ software) to analyze the SEM images. X-ray Diffraction (XRD) (e.g., X′Pert Powder) measurements can be conducted to determine the interlayer spacing of the GO laminates in a dry state. Fourier Transform Infrared Spectroscopy (FTIR) can be used to determine the number of GO bilayers within the laminate while Atomic Force Microscopy (AFM) (e.g., Dimension 3100) can be used to measure the thickness and surface morphologies.
Referring now to
Selection of the best-suited amine or other surface molecule can be determined during the optimization and sieving characterization process. X-ray Photoelectron Spectroscopy (XPS) (e.g., Perkin Elmer 5100) can be employed to evaluate the surface chemistry of GO with Transmission Electron Micrograph (TEM) (e.g., JEM-ARM200CF) determining the GO surface features. Raman spectra (e.g., Horiba LabRAM ARAMIS) can be used to analyze any inhomogeneity developed during GO synthesis. The surface charge of a GO laminate can be tested using a zeta-potential analyzer (e.g., Zetaplus, TA Instruments). For evaluation, simulated plasma can comprise PBS plus 4.0 g/dL HSA and 20 mg/dL bilirubin. Solutions can be incubated overnight prior to dialysis in order to reach bilirubin conjugation equilibrium with HSA. The dialysate can initially comprise 20% HSA to match current commercial systems. For example, the circulation volumes can be 140 mL plasma and 2 mL albumin-rich dialysate in order to match the ratio used by the Gambro MARS® system.
The effectiveness of a GO-based albumin dialysis system to easily release lipophilic species to the albumin dialysate may be adjusted by modifying the GO surface properties such as hydrophobicity, hydrophilicity and surface charge density. In some implementations, the nanospaced GO stack or dispersion may be engineered as an albumin permeable membrane with spacing that rejected larger species (MW>100 kD, D>7 nm) such as immunoglobulin. Albumin-bound and lipophilic toxins can be adsorbed to the GO matrix releasing cleansed albumin in the filtrate, which could then be reintroduced with the blood.
Reducing the pore size and/or separation distance between pores decreases the path length between layers as illustrated in
It should be emphasized that the above-described embodiments of the present disclosure are merely possible examples of implementations set forth for a clear understanding of the principles of the disclosure. Many variations and modifications may be made to the above-described embodiment(s) without departing substantially from the spirit and principles of the disclosure. All such modifications and variations are intended to be included herein within the scope of this disclosure and protected by the following claims.
The term “substantially” is meant to permit deviations from the descriptive term that don'"'"'t negatively impact the intended purpose. Descriptive terms are implicitly understood to be modified by the word substantially, even if the term is not explicitly modified by the word substantially.
It should be noted that materials, ratios, concentrations, amounts, and other numerical data may be expressed herein in a range format. It is to be understood that such a range format is used for convenience and brevity, and thus, should be interpreted in a flexible manner to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. To illustrate, a concentration range of “about 0.1% to about 5%” should be interpreted to include not only the explicitly recited concentration of about 0.1 wt % to about 5 wt %, but also include individual concentrations (e.g., 1%, 2%, 3%, and 4%) and the sub-ranges (e.g., 0.5%, 1.1%, 2.2%, 3.3%, and 4.4%) within the indicated range. The term “about” can include traditional rounding according to significant figures of numerical values. In addition, the phrase “about ‘x’ to ‘y’” includes “about ‘x’ to about ‘y’”.