WO2009042898A1

WO2009042898A1 - Irreversible gels

Info

Publication number: WO2009042898A1
Application number: PCT/US2008/077921
Authority: WO
Inventors: Radhakrishna Sureshkumar; Mukund Vasudevan; Amy Shen; Eric Buse
Original assignee: Washington University In Saint Louis
Priority date: 2007-09-28
Filing date: 2008-09-26
Publication date: 2009-04-02

Abstract

A method for making an irreversible gel by injecting a solution of surfactant and optionally a salt through a microfluidic device, the microfluidic device comprising one or more channels having a packed bed of microparticles and pores there between. The solution is then passed through the packed bed of microparticles; and the gel is collected eluting from the channel after passing the solution through the bed of microparticles.

Description

IRREVERSIBLE GELS

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No. 60/995,971, filed on September 28, 2007. The entire disclosure of the above application is incorporated herein by reference.

GOVERNMENT RIGHTS

[0002] This invention was made with government support under grant Nos. 0552941 and 0404243 from the National Science Foundation. The Government has certain rights in the invention.

BACKGROUND [0003] It is well known that surfactant molecules in solution favorably aggregate and form micelles depending on the concentration of the solute, the critical micelle concentration, and Krafft temperature. The shapes of these micelles vary from spherical/cylindrical at low surfactant concentrations, to lamellar, bilayer, and vesicular structures at higher concentrations. In the case of ionic surfactants, which are charged molecules, the presence of counter-ions significantly alters the inter-molecular electrostatics, thereby influencing the self-assembly process. Hence, the sizes and shape of micelles formed vary considerably, which in turn influences the macroscopic properties of the solution such as the viscosity. This ability of controlling the macroscopic property by small and easy modifications in the solution chemistry has enabled the use of such soft-materials in diverse applications such as the nano-porous material synthesis (sol-gel process), cosmetic industry (as viscosity enhancers), pharmaceutical industry (targeted drug delivery), enhanced oil recovery, and solar energy storage.

[0004] Flo w- induced self-assembly of micelles occurs in certain ionic surfactant solutions when subject to shear. These reversible flow- induced structure (FIS) formed in macroscopic flows have been reported in surfactant solution containing rod- like or worm- like cylindrical micelles in the presence of certain counter-ions at surfactant concentrations below the "overlap threshold", i.e. the surfactant concentration required to form networks or entanglements at equilibrium. To date, such experiments have been conducted in shear flow generated by devices such as concentric cylinders or a cone and plate arrangement. Typically, such solutions exhibit Newtonian rheology at low shear rates, i.e., the viscosity of the solution is practically constant until a critical shear rate γ_c .

[0005] A structure transition referred to as flow induced structure (FIS) formation occurs after a certain inception time period t so that a critical strain γ_c = γ_ct* is applied on the solution. This structure formation is characterized by an increase in the viscosity of the solution (shear thickening), and these structures are qualitatively different than simple micellar aggregates. FIS formation has been observed in several surfactant systems such as cetyltrimethyl ammonium bromide (CTAB), cetyl-trimethyl ammonium chloride (CTAC), cetylpyridinium chloride (CPyCl), and sodium dodecyl sulfate (SDS). Factors such as the type and concentration of surfactant and counter-ion, temperature, and presence of added salts significantly affect the structure formation. For example, in the case of an aqueous solution of the cationic surfactant CTAB, the rheology differs significantly even for chemically similar salts such as sodium salicylate (NaSaI), sodium tosylate (NaTos) and sodium benzoate (NaBz). While NaSaI and NaTos induce shear thickening transitions, solutions with NaBz exhibit only shear thinning behavior, i.e., a decrease in viscosity with increasing shear rates. Rheological experiments on CTAB/NaSal system indicated that for a fixed CTAB concentration, the range of NaSaI concentrations exhibiting shear thickening behavior was rather small. As the molar ratio of salt to surfactant R is increased, the extent of shear thickening decreased, and at higher R-values, pronounced shear thinning behavior was observed. The origin of the shear thickening has been shown to be attributed specifically to heterogeneous nucleation of FIS because of the presence of impurities and/or surface roughness of the geometry used in the experiment.

[0006] Pioneering experiments concerning the evolution of FIS were performed by Pine and co-workers. Liu and Pine performed small angle light scattering (SALS) measurements as well as light scattering microscopy on CTAB/NaSal system in shear flow. SALS patterns revealed the appearance of a distinct streak only in the flow direction whose length and intensity increased corresponding to the shear thickening transition. This also suggested the emergence of rod-like structures aligned along the flow direction with no appreciable correlation in the spacing between the rod-like micelles. Light scattering microscopy of the shear flow between concentric cylinders (Couette cell) indicated bright comb-like structures with the spatial and temporal integrity of a gel, which extended from the stationary inner wall to the rotating outer wall. The presence of gel-like structures imparts an elastic character to the otherwise non-elastic Newtonian solution; hence, positive normal stresses have been observed only when FIS are present. The discontinuity in elasticity of FIS and the Newtonian solution induces an elastic interfacial instability that manifests as temporal fluctuations in the shear as well as normal stresses in this regime.

[0007] FIS formation has been observed in a relatively narrow concentration range of ionic surfactants with added salts. FIS form when shear rate γ >γ_c , and critical strain γ_c > γ_ct* are applied on the solution. It is characterized by an increase in the solution viscosity, the presence of positive first normal stresses and interfacial instability. FIS consist of a highly entangled micellar network that display gel-like behavior.

[0008] In spite of these fascinating characteristics of flow- induced self- assembly, upon cessation of the applied shear γ, FIS disintegrate almost instantaneously into quasi equilibrium structures implying that the FIS formation is reversible. This drawback of FIS being extremely sensitive to the applied γ severely restricts the applicability of these systems in areas such as nano -manufacturing.

SUMMARY [0009] The present technology provides a method for making an irreversible gel. The methods comprise: mixing a salt with a surfactant and thereby forming a salt/surfactant solution; rapidly straining the salt/surfactant solution through a channel having porous media comprising a plurality of microparticles; and recovering the resulting continuous irreversible gel injecting a solution of surfactant and a salt through a microfluidic device. The microfluidic device comprises one or more channels in fluid communication with the salt/surfactant solution. A plurality of microparticles is inserted into the one or more channels to form a packed bed of microparticles and pores there between. The solution is then passed through the packed bed of microparticles, and the gel is collected.

[0010] In another aspect, the present technology provides an irreversible gel obtained by a process which comprises rapidly straining a surfactant through a channel having porous media comprising a plurality of microparticles; and recovering the resulting continuous irreversible gel eluting from the channel. The irreversible gel comprises aligned rod-like micelles and wherein a portion of the rod-like micelles are arranged in three dimensional micellular ropes.

[0011] The irreversible gels described herein have various industrial and medical applications. For example, low dielectric constant film coated with compositions having an irreversible gel, pharmaceutical, personal care and cosmetic compositions containing irreversible gels. Medical devices are also contemplated wherein the devices are implantable and have in some cases, a coating along a surface of the device comprising the irreversible gels of the present technology with one or more therapeutic and medicinal agents admixed therein.

DRAWINGS [0012] The drawings described herein are for illustration purposes only and are not intended to limit the scope of the present technology in any way.

[0013] FIG. 1 is a graphical representation of the deformation rate and strain as a function of porosity with particle size = 30 μm

[0014] FIG. 2 is a graphical representation of the deformation rate and strain as a function of particle size with porosity 0.5.

[0015] FIG. 3, panel A is a Log-log plot of apparent viscosity η app vs. shear rate for CTAB/NaSal solutions with CD = 0.003 M, R = \ (■), and CD = 0.05 M, R = 0.28 (A), where R is the molar ratio of salt to surfactant concentration. Dotted vertical lines

denote the respective critical shear rate γ required for SIS formation. Panel B shows a

Log-log plot of shear stress as a function of time for γ = 100 s-1 (■), 150 s-1 (♦), 200 s-1

(A), and 300 s-1 (•). The respective time periods t required for stress to increase and reach the plateau value, is denoted by the dotted vertical lines. The product γt is the

critical strain γ_c required for SIS formation, γ_c which was found to be constant for a given

concentration of surfactant-salt solution.

[0016] FIG. 4 are micrographs of a montage of shear induced gel formation in a micro channel with W = H = lOOμm. 20 - 50 μm sized particles form a pseudo packed bed at the constriction. The surfactant solution shown in panels a-d with CD = 0.003 M and R = 1 is injected from the right as indicated by the arrows. Flow induced gel form in the pores and exits the bed. Panel e shows a photomicrograph of the gels having a stable interface with the surrounding solution and flow downstream. [0017] FIG. 5. depicts photomicrographs of the irreversible gel exiting the microparticle bed in the channel. Panel f shows a photomicrograph of a gel formed from surfactant solution CD= 0.003 M with R = 1 in 500 μm channel. In this case, sufficient concentration of 50 - 100 μm particles are added to jam one end of the channel to create a microporous medium flow. Panel g is a magnified photomicrograph illustrating the elastic nature of the gel phase is evident from the observation that a particle that accidentally escapes the porous bed is tethered by a gel filament. Arrows in panels (a) - (g) indicate flow direction.

[0018] FIG.6. shows the stability of the irreversible gels made in accordance with the present technology. Panels h and i are photomicrographs of channels having gel trapped in the channel and are observed to be stable after the flow has stopped. Panel h is a photomicrograph of the channel containing an irreversible gel taken 10 seconds after flow cessation. Panel i is a photomicrograph taken of the channel and irreversible gel as in h taken after 1000 sec after the cessation of flow.

[0019] FIG. 7 depicts photomicrographs of atomic force microscope images taken of the dried irreversible gel. Panel a is an unprocessed image of the irreversible gel after being dried using atomic force microscopy. Panel b is a Fourier Transform photomicrograph of the dried gel in panel a. Panel c is a photomicrograph of image seen in panel b filtered illustrating aligned rod-like structures with short range order with holes and channels formed by the alignment that can serve as nano-scaffolds. Panel d is a higher magnification of the image in panel c. The arrows indicate the location and presence of holes within the irreversible gel structure.

DETAILED DESCRIPTION

[0020] The following description of technology is merely exemplary in nature of the subject matter, manufacture and use of one or more inventions, and is not intended to limit the scope, application, or uses of any specific invention claimed in this application or in such other applications as may be filed claiming priority to this application, or patents issuing therefrom. The following definitions and non-limiting guidelines must be considered in reviewing the description of the technology set forth herein.

[0021] The headings (such as "Introduction" and "Summary") and subheadings used herein are intended only for general organization of topics within the present technology, and are not intended to limit the technology of the present technology or any aspect thereof. In particular, subject matter disclosed in the "Introduction" may include novel technology and may not constitute a recitation of prior art. Subject matter disclosed in the "Summary" is not an exhaustive or complete disclosure of the entire scope of the technology or any embodiments thereof. Classification or discussion of a material within a section of this specification as having a particular utility is made for convenience, and no inference should be drawn that the material must necessarily or solely function in accordance with its classification herein when it is used in any given composition.

[0022] The citation of references herein does not constitute an admission that those references are prior art or have any relevance to the patentability of the technology disclosed herein. Any discussion of the content of references cited in the Introduction is intended merely to provide a general summary of assertions made by the authors of the references, and does not constitute an admission as to the accuracy of the content of such references. All references cited in the "Description" section of this specification are hereby incorporated by reference in their entirety.

[0023] The description and specific examples, while indicating embodiments of the technology, are intended for purposes of illustration only and are not intended to limit the scope of the technology. Moreover, recitation of multiple embodiments having stated features is not intended to exclude other embodiments having additional features, or other embodiments incorporating different combinations of the stated features. Specific examples are provided for illustrative purposes of how to make and use the compositions and methods of this technology and, unless explicitly stated otherwise, are not intended to be a representation that given embodiments of this technology have, or have not, been made or tested.

[0024] As used herein, the words "preferred" and "preferably" refer to embodiments of the technology that afford certain benefits, under certain circumstances. However, other embodiments may also be preferred, under the same or other circumstances. Furthermore, the recitation of one or more preferred embodiments does not imply that other embodiments are not useful, and is not intended to exclude other embodiments from the scope of the technology.

[0025] As referred to herein, all compositional percentages are by weight of the total composition, unless otherwise specified. As used herein, the word "include," and its variants, is intended to be non- limiting, such that recitation of items in a list is not to the exclusion of other like items that may also be useful in the materials, compositions, devices, and methods of this technology. Similarly, the terms "can" and "may" and their variants are intended to be non-limiting, such that recitation that an embodiment can or may comprise certain elements or features does not exclude other embodiments of the present technology that do not contain those elements or features.

[0026] Although the open-ended term "comprising," as a synonym of terms such as including, containing, or having, is use herein to describe and claim the present invention, the invention, or embodiments thereof, may alternatively be described using more limiting terms such as "consisting of or "consisting essentially of the recited ingredients.

[0027] The present technology provides methods for producing irreversible gels from dilute surfactant/salt solutions, by imposing a very high strain upon the surfactant/salt solution over a very short time period. Conventional methods have been able to obtain a gel phase dispersed in a solvent/solution phase, referred to as flow-induced structures (FIS), by the application of strain. However, FIS have been known to disintegrate once the strain (flow) is removed. In contrast, the inventors of the present technology have unexpectedly found that the methods provided herein afford the production of a gel that is irreversible and wherein the gel phase remains stable even after several months. [0028] Unlike conventional sol-gel processes, the methods of irreversible gel formation in accordance with the present technology do not involve or require the addition and evaporation of solvents such as alcohols and extreme pH conditions. Hence they provide superior control of the gel structure and are more compatible with biological agents. Moreover, under previously described techniques, much higher concentrations of surfactants were required to produce the gels. The methods for producing the irreversible gels of the present technology allows for efficient utilization of the raw materials, i.e., surfactant, and/or salts, e.g., gels can be formed with SDS at weight percentage as low as 0.6, whereas typical consumer products (e.g. shampoo) may contain up to 14% surfactant by weight.

[0029] In some embodiments, microfluidic devices can be used to produce stable and irreversible FIS or gels. Microfluidics are very convenient to handle, easy to fabricate, cost efficient, reliable and portable, and since they can be made transparent, complete visualization of the process is possible. In some embodiments, other devices can be implemented to generate larger quantities of irreversible gels (ranging from milliliter to liter quantities) using the principles of the present technology. Methods for producing irreversible gels consisting of providing a surfactant/salt solution under severe strains for relatively short periods of time can also be scaled up. The scaled-up geometry can include essentially a packed bed with a sufficiently long entrance section to allow for pre-shearing the fluid. Pre-sheared fluid can be passed through the packed bed affixed to the end of this tube. The bed can contain 30 μm particles with porosity = 0.5. The flow rate can be controlled via a pump such that the critical deformation rate is achieved in the tube. Similarly, the length of the packed bed can be sufficiently large to achieve the critical strain.

Surfactant Solutions

[0030] The present technology provides for irreversible gels that are composed of a surfactant and optionally a salt solution. In some embodiments, combinations of two or more particularly effective surfactants can be mixed to form the dilute surfactant component of the composition. The ionic surfactant and a compatible counter ion in the form of a salt can be employed to form irreversible gels. The gels contain rod or cylindrical shaped micelles, and can be formed from ionic, non- ionic, and zwitterionic surfactants with the optional addition of various salts and different solvents. Any surfactant system that displays flow- induced structure transition can be used. Hence, the present technology encompasses all classes of surfactants.

[0031] In some embodiments, the surfactant can include organoammonium compounds, organoferrocenium compounds, organopyridinium compounds, organoamine oxides, glucosides, cetrimide, cetyltrimethyl ammonium bromide (CTAB), (DTAB), benzalkonium chloride, DDA (dimethyl dioctodecyl ammonium bromide), DOTAP, cetyl-trimethyl ammonium chloride (CTAC), Cetylpyridinium chloride (CPyCl), lauryldimethylamine oxide (LDAO), bis(2- ethlyhexyl) sulfosuccinate sodium salt, sodium dodecyl sulfate (SDS), SLS, DSS (disulfosuccinate), sulphated fatty alcohols, sodium deoxycholate (DOC), N- lauroylsarcosine sodium salt, and the like, and combinations thereof.

[0032] The concentration of each surfactant can vary depending on the species of surfactant/salt combinations required to form micelles having specific chemical properties suitable for a particular application. In some embodiments, the concentration (C_D) of the surfactant or plurality of surfactants in the solution to be treated can range from about 0.1M to about 0.00001M, from about 0.01M to about 0.00001M, from about 0.001 to about 0.00001, from about 0.0001 to about 0.00001, from about 0.1M to about 0.0001M, from about 0.1M to about 0.001M, or from about 0.1 M to about 0.01M. [0033] Surfactants used to make the irreversible gels can be procured commercially from various chemical vendors, for example, Fluka (Milwaukee, WI, USA), Sigma-Aldrich (St. Louis, MO, USA), and Dow Chemical (Midland, MI, USA). In some embodiments, the surfactant can be mixed with purified water, for example, Millipure Water (resistance greater than 17 MΩ).

Salt Solution

[0034] The surfactant/salt systems contemplated in the present technology can include any salt capable of providing counter ions to the surfactant micelle to reduce the electrostatic Debye layer which also aids the inter-micellar interactions. The salt can function to screen electrostatic repulsion to promote micelle network formation. Given a surfactant, one of ordinary skill can find salts that are ideal to do this, which can be determined by equilibrium studies. [0035] Gel formation can be expected from solutions that contain rod-like micelles. Addition of salt helps reduce the surfactant concentration at which such rod- like phases form.

[0036] The surfactant/salt combinations can include sodium docecyl sulfate (SDSydimethyltetradecylamine oxide (TDMAO), and CTAB/NaSal. These surfactant/salt combinations are canonical and many other surfactant salt combinations can be formulated by those of skill in the art of surfactant chemistry. The concentration of salt to be added to aqueous surfactant solutions can be calculated from a predetermined molar ratio of salt concentration to surfactant concentration denoted by the symbol R. The ratio of the salt concentration to surfactant concentration (R) can range from 10 to 0.01 to 0.01 to 10 or expressed numerically 10:0.01-0.01 : 10. The surfactant and salt components are mixed in a fluid to form the gel prior to shearing. The gel components can be mixed with water to form aqueous solutions or they can be solvated in any compatible fluid or solvent.

[0037] Mixture of the salt and the surfactant(s) can be accomplished using a commercial mixer, such as a shaker and equilibrated prior to placing the solution in a microfluidic device or other micelle-straining device.

[0038] In some gels, the initial surfactant is not mixed with a salt and is subsequently strained through a microfluidic device, tube, funnel or channel having a packed bed of microparticles to form an irreversible gel. When using a surfactant alone, gelation can occur without salt albeit at higher concentrations of the surfactant. Irreversible gels can be formed with surfactants such as CTAB, CpyCl and SDS. The concentrations can be varied, but typically are in the millimolar range.

Methods of Forming an Irreversible Gel [0039] Without wishing to be bound by theory, it is believed that the process for producing an irreversible gel can be explained with the use of the Hagen-Poiseuille law, wherein the flow rate (F = volume of fluid flowing per unit time) is proportional to the pressure difference between the ends of the channel or tube and the fourth power of its radius r as shown in equation 1 , F = πΔPr⁴ (1)

can be used to determine the appropriate flow rate (F) and size of fluidic channels necessary to obtain a desired shear rate (γ ). The factors responsible for irreversible gel formation are the instantaneous application of both the critical flow deformation rate and the critical strain. As the salt concentration is increased for a given surfactant concentration, the critical deformation rate decreases and so does the critical strain. Hence, the irreversible gels can be formed at lower deformation rates (or strains) by increasing the salt concentration. Gels can be formed from extremely dilute surfactant- salt solutions (above the critical micelle concentration CMC) to concentrated systems. In some embodiments, the method of producing gels irreversibly can be performed using a microfluidic device although other device geometries can be used.

[0040] The irreversible gels can be formed after passing a dilute concentration of surfactant /salt solution through a microfluidic device channel packed with microparticles. The microfluidic devices that can be used to form the irreversible gels can have rectangular micro-channels with heights varying from about 30-500 μm and widths varying between 10 - 100 μm. The channels of the microfluidic device can be made smaller by inserting poly disperse (0.01-300 μm) glass particles (Polysciences, Inc., Warrington, PA, USA) inside the channels of the device. These particles accumulate at a constriction in the channel and form a packed bed. The pores in the bed have diameters that range from less than 1 micron to about 50 microns. Specifically, the microchannels of the microfluidic device can be packed with materials such as spheres. A small amount of these particles can be added to one or more channels prior to injecting the surfactant/salt solution, for example, CTAB/NaSal solution.

[0041] The channels can be designed with a constriction at one end to hold the microparticles. Upon injection of the surfactant/salt solution at the calculated flow rate (such that γ ≥γ_c), these particles can be accumulated near the constriction and form a pseudo-packed bed of porous microparticles. In some embodiments, the microparticles can be of uniform or non-uniform size and can be packed into the microfluidic channel, funnel, or tube (e.g. a capillary tube or glass, ceramic or plastic tube of various diameters and wall thicknesses) using standard methods in the art, including vacuum, gravity, and pressure.

[0042] The volume of the beads governs the porosity of the bed. The size of the particles as well as the volume (porosity) can be changed as long as they allow for the critical factors for irreversible gel formation. As shown in FIG. 1, plots of the deformation rate and strain as a function of the porosity and particle size determined via reliable and widely used mathematical models for porous medium flow. For the solution with CTAB concentration 0.003 M with molar ratio R = NaSal/CTAB = 1, the critical deformation rate is around 10 s^"1, while the critical strain is roughly 4000 (shown as the dotted black line). The channel, or device used to pass the salt/surfactant solution can employ solid particles in an amount sufficient to form a bed porosity of about 0.01 to about 1.0, and can include porosities of 0.4 to 1.0 for ideal spherical particles, wherein a porosity of 0.5 can be sufficient to achieve the critical strain required for FIS formation, for example, in microfluidic devices. Where not all of the surfactant/salt solution is processed through the pores to form a gel, one feature evident from the interaction between the solution and gel is that there is no interfacial instability between the gel and the surfactant solution. As long as the flow is imposed, the irreversible gels are continuously formed and move with the flow. For 30 μm particles (Fig.l), although all porosity values give deformation rates above 10 s^"1, porosities below 0.5 give strain values above 4000. However, it has been shown in the literature that the minimum porosity achievable using mono-disperse spherical particles is roughly 0.4 (alternately, the use of poly-disperse particles can be used to obtain lower porosities). Hence, a porosity value of between 0.4 and 0.5 can be chosen. In Fig. 2, with a given porosity of 0.5, particle sizes below 40 μm provide sufficient strain for the irreversible gel formation. Hence, smaller particles than 40 microns can also be used. The porosity of a bed is defined as volume of particles/volume of bed. [0043] The size of the pores between microparticles can range from about 1 nm to about 50 μm in size. The distribution of the pores can be uniform or random. The pore sizes can be uniform or mixed. Hence, the flow area within the pores is several orders of magnitude smaller than the flow area of the micro channel. While the solution is already pre-sheared as it passes through the inlet tubes and channels within the microfluidic device, when the salt/surfactant solution enters the pores, it experiences a sudden and steep increase in the shear rate and strain by several orders of magnitude. This exerts an instantaneous, but extremely large strain on the surfactant micelles thereby causing a thermodynamically irreversible phase transition to a gel. The surfactant/salt solution can be injected into the channels by any means of fluid transfer, for example, by means of a syringe, at flow rates such that shear thickening transition (i.e. viscosity enhancement due to gel formation) occurs.

[0044] In some embodiments, gel formation can be verified with different channels using different sizes of microparticles. The gel formation in a larger channel of 500 μm with 50-100 nm sized particles has been shown, wherein the gel formation occurs at many points within the pores, after which, they move along in a worm-like motion through the channel. This gel formation can also be achieved for other concentrations of the surfactant CTAB and NaSaI salt as well as other surfactants such as CPyCl and SDS. All these surfactants exhibit shear induced gel formation. [0045] Others have shown that FIS formed in conventional rheometers cannot be sustained even for 2 seconds after the flow is stopped. Even after the flow of solution is stopped in the devices of the present technology, the irreversible gels formed in the channels remain intact over time. Without wishing to be bound by theory, it is generally believed that the gel irreversibility and stability originate due to the conformational changes experienced by the micelles as they undergo both stretching and extension. It is well known that macro molecules like DNA undergo a variety of conformations in shear and extensional flows. At the pores, there is an instantaneous application of large magnitudes of shear and extension. The frequency and the amount of stretching and orientation experienced by the micelles are possibly extremely large in such conditions, because of which micelles experience tremendous amounts of instantaneous strain that quenches them in a shear induced thermodynamically irreversible state.

[0046] Irreversible gels form when there is an instantaneous application of both the critical deformation rate and critical strain. The flow rate of the solution through the micro fluidic channels having packed microparticles governs the deformation rate in the channel, and has no effect on the critical strain. Hence, the flow rate can be such that the critical deformation rate is achieved. Flow rates can vary depending on the surfactant, the size of the channel, tube or device used to strain the surfactant through the packed bed. In some structures the flow rate Q can range from 0.1 mL/hr to about 100 mL/hr, or from about 0.5 mL/hr to about 100 mL/hr, or from about 1 mL/hr to about 100 mL/hr, or from about 5 mL/hr to about 100 mL/hr, or from about 10 mL/hr to about 100 mL/hr, or from about 0.1 mL/hr to about 50 mL/hr, or from or from about 0.1 mL/hr to about 20 mL/hr, or from about 0.1 mL/hr to about 10 mL/hr, or from about 0.1 mL/hr to about 5 mL/hr, or from about 0.1 mL/hr to about 1 mL/hr.

[0047] A specified length of the packed bed is required for achieving the critical strain.

[0048] The Kozeny-Carman equation; S= 150Q (1-εΫ (2) and

D_p ²H ε³ γ = 150WL (l-ε)² (3)

D_p ² ε³ can be used for calculating the critical shear and strain in the packed bed for a given flow rate in the pipe. The shear viscosity as a function of shear rate of the two CTAB/NaSal surfactant/salt solutions used in this study is given in Fig. 3A. The surfactant concentrations (CD) used were 0.003 M and 0.05 M, with the molar ratio of salt to surfactant R = I and 0.28, respectively. Here Q is the flow rate, D_p is the particle diameter, and L is the length of the porous bed with porosityε. For some devices, D_p ~ 30 μm and the porosity ε, a flow rate Q = 5mL/hr gives S ~ 0(10⁶) s^"1 and γ ~ 7000 in approximately 0.001 s. When the operable strain rate is of a million or so inverse seconds, the critical strain is several thousands (dimensionless), hence the time scale over which the material is strained is on the order of milliseconds. Knowing the strain achieved in the packed bed, one of ordinary skill in the art can either increase or decrease its length to satisfy the critical shear rate if a shear rate γ > γ_c was applied to the solution, the stress increased after some time period and reached a statistically stationary plateau value. The time needed for the stress to rise, or alternatively, the inception time for FIS formation decreased as γ was increased. This is illustrated in Fig. 3B, where, for a solution with CD = 0.05M and R = 0.28, applied shear rates of 100, 150, 200 and 300 s-1 can be used. [0049] Because of the gel's properties, namely, irreversibility and stability, the gels can be collected in vials after passing or passage through the channel containing microparticles as shown in FIG. 4, and independently characterized.

[0050] Other devices can be used to provide the requisite strain required for the transitioning of the surfactant/salt solution phase to a gel phase, for example, where flow area is abruptly reduced such as forcing the solutions through a needle connected to a syringe. To scale up the production of irreversible gels from surfactant/salt solutions described and referred to herein, irreversible gel formation can be accomplished in any device provided that the critical deformation rate and critical strain be exerted on the solution instantaneously. Hence, various devices having the scaled-up geometry should allow for this. In some embodiments, a scaled up device can include a packed bed of microparticles to macroparticles through which a sufficiently pre-sheared fluid would pass - just as the fluid passes though the tube and micro channel before it passes through the porous bed within the micro fluidic device.

[0051] To scale up the devices that can be used to produce the irreversible gels, a larger diameter tube (tube ID = 5mm) can be used as the channel for irreversible gel production. The microparticles can include 30 μm particles with a porosity of about 0.5. A pump can be used with a flow rate such that the critical deformation rate is achieved in the tube. The tube can be long enough to pre-shear the fluid (similar to the micro fluidic set-up). Similarly, the length of the packed bed can be sufficiently large to achieve the critical strain instantaneously. From the viscosity enhancements observed, it is contemplated that solution to gel phase transition could also be created in such a fashion. Hence, in some embodiments, the scaled up devices can incorporate surfactant/salt solutions that can be subjected to sudden high flow deformations to manufacture gel phases that have a variety of applications listed below.

[0052] The irreversible gels produced using the methods of the present technology are distinct from other thermally irreversible gels produced using shearing different methods described in the art. The gels obtained from the methods of the present technology can consist of highly aligned micelles with a short-range order. Phase transition in a larger channel of 500 μm with 50-100 μm sized particles is shown in FIG. 5 panel f. The gel phase is "sticky" or elastic as seen from FIG. 5 panel g where a particle that accidentally escapes from the constriction is tethered by a strand of the gel. In the case of gels formed in microfluidic channels, even after flow stoppage, the gels formed in the channels remained intact over time. In FIG. 6, panels h and I, images of the CTAB/NaSal gel (CD = 0.003M, R = 1) in a 150 μm channel soon after the flow was stopped the flow (0 s) and after 1 ,000 s respectively are shown. [0053] The gels generally have aligned phases of rod-like micelle superstructures. The rod or cylindrical like micelles have general dimensions ranging from 10-500 nm in length and 3-30 nm in diameter. 10-20% of these rod- like micelle structures are fused and form rod superstructures after extrusion and can form super micellular ropes having an average length of about 200 nm and diameters ranging from about 4-12 nm. The rod superstructures are self-assembled in the gel (See FIG. 7, panels a and c). The super micellular ropes have unique geometric properties. The super micellular ropes can be aligned in three- dimensional stacks. Each rope separated along a vertical axis by about 5-10 nm. Due to the three-dimensional stacking, the ropes can be intertwined forming partial coiled regions. The partial coiled regions provide spaces or holes shown in FIG. 7, panel d that can entrap various materials for controlled release and delivery. The holes have an approximate size of about 10-30 nm. Atomic Force Microscopy (AFM) analysis of the salt/surfactant solution when dried failed to reveal any short - range order, indicating that the irreversible gels and the salt/surfactant solution are qualitatively different (See generally, FIG. 7, panels a-d). The rod superstructures of the present technology can have lengths and widths almost an order of magnitude smaller than those reported by Liu et al. (Phys. Rev. Lett. 77:2121-2124 (1996)).

[0054] The present gel compositions are made with salt/surfactant solutions that are capable of forming rod-like micelles. Surfactant solutions that form spherical micelles under extrusion cannot be used to form the irreversible gels of the present technology. Hence, only surfactants, which are capable of forming rod-like micelles at a concentration above the critical micelle concentration, are contemplated in the present methods.

Methods of Characterizing the Irreversible Gel

[0055] The structural characteristics of the gel can be determined using several physical-chemical methods. In some embodiments, the structure of the irreversible gel can be determined using cryogenic transmission electron microscopy (Cryo-TEM), small angle light scattering (SALS), light scattering microscopy, NMR velocimetry, and AFM. Because of irreversibility and stability, the gels can be collected in vials after exiting the channel and independently characterized or processed further for additional applications. In some embodiments, since the gel and the surfactant solution can come out of the pores, and hence the collected sample can contain both these phases, centrifuging these samples for a minute reveals that the gels are suspended within the surfactant solution. In some embodiments, characterization of the gel structure can be determined by withdrawing a predetermined volume of the gel layer and carefully pipetting the gel onto clear silicon wafer and dried at room temperature and analyzed using AFM.

Applications for Irreversible Gels

[0056] The present technology provides irreversible gels useful in various industrial and medical applications. For example, the stable nature of the gel phase with the small holes and channel sizes can be conveniently used as stable scaffolds to make nano and micro-porous structures with large effective surface areas. The applicability of the irreversible gels to preexisting nanotechnologies, and for use in the personal care field is enormous. For example, with the addition of quantum dots, these scaffolds can be used in microelectronics and remote sensing.

Biomedical Applications

[0057] One of the many advantages obtained by the methods described herein includes sol-gel transition, which can be accomplished without the addition of alcohols, rendering the process biocompatible for the development of nano biosensing and biodelivery devices. Hence, bioengineered devices, such as implantable drug-delivery stents, microfluidic devices, biological Micro-Electro-Mechanical-Systems (bioMEMs) and implantable drug-delivery devices can all incorporate the present irreversible gels.

[0058] The production of irreversible gels containing drugs, medicaments and other therapeutic agents can be performed using biocompatible surfactants and salts and subsequently used in medical applications such as targeted drug delivery and in medical/therapeutic agents and devices, including neural and cardiac stents and other drug delivery devices. The irreversible drugs can be made to contain various degrees of porosity, which makes the gel ideal for drug delivery. One useful application of such a drug delivery agent is in coatings on various medical devices. Such medical devices can include a therapeutically effective amount of a therapeutic agent that may be incorporated into or onto the medical device. A therapeutic coating for a medical device can include a composition comprising: a fluid irreversible gel obtained by a process which comprises rapidly straining the surfactant through a channel having porous media comprising a plurality of microparticles and recovering the resulting continuous irreversible gel, the irreversible gel comprising aligned rod-like micelles and wherein a portion of the rod- like micelles are arranged in three dimensional micellular ropes; and a cosmetically or pharmaceutically acceptable excipient.

[0059] The implantable medical device can be coated with the therapeutic composition the composition further comprising a pharmaceutical drug, a biologic, a nucleic acid, an antibiotic and combinations thereof. Medical devices contemplated for use with the therapeutic composition using the irreversible gel of the present technology can include a stent used to open stenosed arteries and veins. The stent can be a solid or flexible biocompatible material such as plastic, rubber or surgical metal or metal composites. The stent can be coated with a therapeutic composition that functions as a drug delivery composition including an irreversible gel in admixture with a pharmaceutical drug.

[0060] The implantable stent can be used for neural or cardiac applications.

The stent can also be coated with a therapeutic composition having one or more pharmaceutical drugs for example one or more beneficial substances, e.g., those which aid the natural healing process and/or prevent restenosis. Pharmaceutical drugs that can aid in preventing restenosis and clot formation include anti-clotting and anti-plaque agents, e.g., naproxen and ibuprofen. Suitable clot-preventing drugs include clopidogrel, heparin, heparan sulfate, low molecular weight heparins, danaparoid, fondaparinux, hirudin, bivalirudin, aspirin and Coumadin.

[0061] Since the initial solution has low viscosity (approximately 1 cP), the processability of these solutions for a variety of applications can be readily evident.

Cosmetic and Personal Care Applications [0062] The irreversible gels described herein can also be used in detergents, shampoos, and cosmetics as thickeners. Novel shampoo and/or conditioner compositions comprising the irreversible gels of the present technology are envisaged. As described above, the irreversible gels have been shown to possess nano-channels and nano-pores or holes. Such a structured network can afford unique opportunities to incorporate additional hair and skin conditioners into the nanostructures. In some embodiments, the hair care products comprising the irreversible gels can include a dispersed gel network phase having detersive surfactants (anionic, cationic, amphoteric, zwitterionic, and non- ionic), fatty acids, polymers, polysaccharides, celluloses, emulsifϊers and other known hair and skin components. The irreversible gel scaffolds and voids included in shampoo and conditioner compositions of the present technology can be used to provide conditioning benefits along with stable, reproducible viscosity build, improved pouring with no drips, soft hair-feel effect, improved textural properties and hair that feels conditioned. A typical composition can include (v/v %): Water 87%, sodium lauryl sulfate 7.8%, sodium chloride 0.8-1.4%, cocamidopropyl betaine 0.8%, laureth-3 2- 2.5%, irreversible gel of the technology 0.5%, preservative q.s and parfum q.s. Other cosmetic and personal care compositions are known to those of ordinary skill in the art. The irreversible gels of the present technology can be substituted for similarly functioning components such as thickeners, and rheology modifiers. Other personal care and cosmetic compositions useful in the formulation of similar products with the inclusion of the irreversible gels of the present technology are described in pharmaceutically acceptable excipient, such as the ones described in Gennaro et al., Remmington: The Science and Practice of Pharmacy, 20^th Edition, Lippincott, Williams and Wilkins; 2000; see especially part 5: pharmaceutical manufacturing. Suitable excipients are made available; e.g., in the Handbook of Pharmaceutical Excipients, 2^nd Edition; Editors A. Wade and P. J. Weller, American Pharmaceutical Association, Washington, The Pharmaceutical Press, London, 1994, which are hereby incorporated in their entirety. Cosmetic excipients can include one or more of talc, mica, silicas, kaolin, zinc oxide, calcium carbonate, magnesium carbonate phosphate, starch and its derivatives, nylon, polyethylene, acrylic (co) polymers, thickeners, texturisers, conditioning agents, softeners, complexing agents, perfumes, pearlising agents, preservatives, acidifϊers and purified water among others well known in the cosmetics and personal care arts.

Hydrocarbon Recovery Applications

[0063] The irreversible gels produced in accordance with the methods herein, can find wide applicability in gelling solutions that are used for various processes in hydrocarbon (crude oil and natural gas) recovery and treatments. The irreversible gels of the present technology can be added to microparticulate materials such as to enable various primary and secondary casing operations in producing subterranean well bores. Filling fluids comprising the irreversible gels of the present technology can be admixed with fine particulate materials having an average particle size smaller than the average particle size of the packing particulate material such as sand, gravel, limestone and the like, so that the filling particulates can plug at least a portion of the interstitial spaces between the packing particulate material in cement packs. The filling particulate material used can have an average particle size of less than about 100 microns. These filling materials comprising irreversible gels can be used to fill cracks and other deficits in cement casings used to tap into hydrocarbon sources. The viscosity of the present gels can be controlled based on the degree of strain applied and the concentrations of the surfactant/salt solutions used. Carrier solutions with controllable viscosity properties can be particularly useful for controlled packing of fine cracks and other deficits in cement casings used for hydrocarbon recovery.

[0064] Other hydrocarbon recovery applications can include the use of the irreversible gels to penetrate oil-bearing portions of a formation and displace hydrocarbons from hard to recover locations by injecting the irreversible gels into the oil bearing formation under pressure, particularly during secondary and tertiary recovery processes. Methods for using the irreversible gels in hydrocarbon recovery and exploration are exemplified in U.S. Patent Application Publication No. 2008/0202744 by Crews, J.B., et al. published August 28, 2008.

Photonics and Quantum Electronics Applications

[0065] In some embodiments, the irreversible gels of the present disclosure are advantageous in that they can be formed without the addition of alcohols. The present irreversible gels can have a level of porosity that can be controlled, depending on the surfactant/salt combination used, the concentration of the various constituents and the degree of strain applied to form the gels. Moreover, the presence of fine nano- and micro-pores within the gel structure makes them ideal candidates for electronic applications and uses both in bulk and as thin films. In some embodiments, these uses can include low dielectric constant thin films (particularly on semiconductor substrates), miniaturized chemical sensors, thermal isolation structures, and thermal isolation layers (including thermal isolation structures for infrared detectors). As a general rule, many low dielectric constant thin films prefer porosities greater than 60%, with critical applications preferring porosities greater than 80 or 90%, thus giving a substantial reduction in dielectric constant. In some embodiments, the irreversible gels of the present disclosure present ideal substrates for nano-detection devices.

[0066] In still further embodiments, the irreversible gels can be combined with silica particles and/or conductive particles which can be designed and manufactured into thin film coatings, including some types of optical coatings, some types of protective coatings, and some types of porous coatings. Examples of such thin film coatings can include antireflective (AR) coatings, which can require a wide range of porosities. The porosities in AR coatings will typically range from 20% porous to 70% porous, although higher porosities (above 90%) may be useful where there is adequate surface protection, and lower porosities (down to 10%, or below) may be useful in high performance coatings or coatings on substrates with a high index of refraction. In some single layer AR coatings, it may be preferable to use irreversible gels with porosities between 30% and 55%. Higher performance, multi-layer AR coatings will prefer denser layers (e.g., porosity between 10% and 30%) next to the substrate, and less dense layers (e.g., porosity between 45% and 90%) next to the air interface. For higher strength/toughness applications, especially where high strength and surface area are the primary goals, it may be preferable to use a low porosity gel with a porosity between 20% to 40%. Other thin film coatings may need the lowest density practical. In other examples, bulk irreversible gel uses can include nanoporous (e.g., molecular) sieves, thermal insulation, catalyst supports, adsorbents, acoustic insulation, and opti-separation membranes.

EXAMPLES

Example 1. Irreversible Gel Formation In Microfluidic Devices

[0067] Two aqueous solutions of surfactant CTAB (Fluka) with added salt NaSaI (Sigma Aldrich) were prepared using nano-pure water with a resistance greater than 17.9 MΩ . The solutions had CTAB concentrations CD = 0.003 M and 0.05 M, respectively, with molar ratio of salt to surfactant R = I and 0.28, respectively. A shaker was used to mix the contents after which the solutions were equilibrated for three days before being used for analysis. The samples were stored at room temperature without direct exposure to sunlight. Rheological experiments were performed using TA Instruments AR 2000 constant stress and strain rheometer, using a cone and plate geometry with a diameter of 60 mm (cone angle 0°59'49", truncation 27μm). The torque range of the rheometer was 0.1 μNm - 200 μNm, and the minimum stress measurable was 0.0008 Pa. Temperature was controlled at 24°C by a Peltier plate. A solvent trap was used to minimize evaporation. At the end of each experiment, the Peltier plate was flushed with water to remove the sample and then dried and cleaned using Isopropyl alcohol (Sigma Aldrich) before adding a new sample. Extreme care was taken to ensure reproducibility, and all results reported were averaged over three runs. For the microfluidic experiments, soft-lithography was used to etch a microchannel pattern on to a silicon wafer. A PDMS mixture was prepared with 10:1 w/w ratio of silicone elastomer base Sylgard 184 to its curing agent (Dow Corning) and then poured over the pattern in a petri dish, heated at 60⁰C for an hour to harden the PDMS, and then carefully cut. Holes were drilled at the channel inlet and outlet. A clean and dry glass slide and the patterned side of the PDMS were placed in a plasma chamber at 300 mTorr for a minute to increase their surface energy and facilitate covalent bonding, after which they were tightly pressed against each other to form the micro-fluidic device. A small quantity of poly-disperse (20-100 μm) glass particles (Polysciences, Inc.) was inserted into the channel holes by means of forceps. Subsequently, polyethylene tubes (Becton Dickinson and Co.) were then inserted into the holes. 1 ml medical grade syringes (Becton Dickinson and Co.) with 27 G 1 2 needles (BD Becton Dickinson and Co.) were used to inject the surfactant solution into the micro channel by means of a Harvard Apparatus syringe pump. To eliminate contamination from the lubricant oil used in the syringes, all syringes and needles were sonicated in Isopropyl alcohol (Sigma Aldrich), rinsed thoroughly with nano-pure water, and dried at 120⁰C for a day before being used for experiments.

[0068] Leica DM IRB inverted fluorescence microscope with a high speed

Photron camera (60 frames per second) was used to observe the flow within the micro channel. AFM was performed in ambient conditions using a Molecular Imaging PicoScan AFM with a tip of spring constant 0.2 N/m. The measured lateral (x - y) resolution was ~ 10 nm and z-height resolution was ~ 0.2 nm.

Claims

CLAIMSWhat is claimed is:

1. A method of making an irreversible gel comprising: straining a surfactant through a channel having porous media comprising a plurality of microparticles located within the channel, and recovering the resulting irreversible gel.

2. The method according to Claim 1, wherein the surfactant further comprises a salt.

3. A method according to Claim 1, wherein the porous media comprises a packed bed of microparticles having nano or microsized pores therebetween.

4. The method according to Claim 3, comprising straining the surfactant by injecting the surfactant into a plurality of said channels.

5. The method according to Claim 3, wherein packed bed has a porosity ranging from about 0.01 to about 1.0.

6. The method according to Claim 3, wherein the packed bed has a porosity ranging from about 0.3 to about 0.6.

7. The method according to Claim 3, wherein the nano or microsized pores between the microparticles have a pore size ranging from about 1 nm to about 50 μm.

8. The method according to Claim 1, wherein the microparticles are spherical microparticles having a size ranging from about 1 μm to about 300 μm.

9. The method according to Claim 1, wherein rapidly straining comprises passing the surfactant through the porous media bed at a flow rate that is capable of inducing a critical strain on the solution sufficient to induce a thermodynamically irreversible phase transition to a gel.

10. The method according to Claim 9, wherein the critical strain is calculated using a Kozeny-Carman equation.

11. The method according to Claim 2, wherein the salt and the surfactant are present in a weight ratio of 10:0.01 to about 0.01 : 10.

12. The method according to Claim 9, wherein the surfactant does not form spherical micelles upon hydration with an aqueous solution.

13. The method according to Claim 1, wherein the channel is part of a structure selected from the group consisting of a microfluidic device, a tube, a syringe, a funnel and a conical device.

14. An irreversible gel obtained by a process which comprises rapidly straining a surfactant through a channel having porous media comprising a plurality of microparticles, and recovering the resulting continuous irreversible gel, wherein the irreversible gel comprises aligned rod-like micelles arranged in three dimensional micellular ropes.

15. The irreversible gel according to Claim 14, wherein the surfactant is mixed with a salt to form a salt/surfactant solution prior to straining.

16. The irreversible gel according to Claim 14, wherein the surfactant is selected from the group consisting of organoammonium compounds, organoferrocenium compounds, organopyridinium compounds, organoamine oxides, glucosides, cetrimide, cetyltrimethyl ammonium bromide (CTAB), dodecyltrimethylammonium bromide (DTAB), benzalkonium chloride, dimethyl dioctodecyl ammonium bromide (DDA), 2- Dioleoyl-3-Trimethylammoniurn-Propane (DOTAP), cetyl-trimethyl ammonium chloride (CTAC), Cetylpyridinium chloride (CPyCl), lauryldimethylamine oxide (LDAO), bis(2-ethlyhexyl) sulfosuccinate sodium salt, sodium dodecyl sulfate (SDS), sodium lauryl sulfate (SLS), disulfo succinate (DSS), sulphated fatty alcohols, sodium deoxycholate (DOC) and N-lauroylsarcosine sodium salt.

17. The irreversible gel according to Claim 15, wherein the salt/surfactant solution comprises sodium salicylate and cetyltrimethyl ammonium bromide.

18. The irreversible gel according to Claim 14, wherein the concentration of the surfactant in the irreversible gel ranges from about 0.00001M to about 0. IM.

19. A low dielectric constant film coated on at least a portion of a semiconductor substrate with the irreversible gel of Claim 14, said film comprising a porosity of greater than 60%.

20. A composition comprising:

(a) a fluid irreversible gel obtained by a process which comprises rapidly straining the surfactant through a channel having porous media comprising a plurality of microparticles and recovering the resulting continuous irreversible gel, the irreversible gel comprising aligned rod-like micelles and wherein a portion of the rod-like micelles are arranged in three dimensional micellular ropes; and

(b) a cosmetically or pharmaceutically acceptable excipient.

21. An implantable medical device coated with the composition of Claim 20, wherein the composition further comprises a pharmaceutical drug, a biologic, a nucleic acid, a therapeutic agent, or combination thereof.

22. The implantable medical device of Claim 21, wherein the medical device is a stent, and the composition comprises a pharmaceutical drug.

23. The implantable medical device of Claim 22, wherein the pharmaceutical drug is a clot-preventing drug selected from the group consisting of clopidogrel, heparin, heparan sulfate, low molecular weight heparins, danaparoid, fondaparinux, hirudin, Bivalirudin, aspirin and Coumadin.

24. The implantable medical device of Claim 23, wherein the stent is a cardiac stent or a neural stent.