Systems and methods for continuous-flow laser-induced nucleation

In general, the systems and methods described in this application relate to laser-induced nucleation in continuous flow. A method of laser-induced nucleation in continuous flow includes injecting a saturated solution, undersaturated solution, or supersaturated solution through an inlet of a device. The method can include converting the saturated solution or undersaturated solution into supersaturated solution by changing a temperature of the saturated solution or undersaturated solution. The method can include passing one or more laser pulses through the supersaturated solution within the device. The method can include flowing the saturated solution, undersaturated solution, or the supersaturated solution through an outlet of the device.

TECHNICAL FIELD

The present disclosure generally relates to the field of crystallization, and more specifically, to systems and methods for laser-induced nucleation.

BACKGROUND

Crystallization has been used in science and commerce as an efficient method of concentrating and purifying chemicals. Nonphotochemical laser-induced nucleation (NPLIN) is a type of nucleation method in which nucleation is achieved by the action of light on matter. NPLIN has been observed in various aqueous solutions, including urea, glycine, simple salts such as alkali halides, and proteins. The NPLIN of carbon dioxide bubbles from carbonated water has also been observed.

Three mechanisms have been proposed to account for NPLIN. In the optical Kerr effect mechanism, the applied optical electric field induces the alignment of solute molecules in disordered solute clusters, lowering the barrier to nucleation. In the dielectric polarization (DP) model, the applied electric field lowers the energy of slightly sub-critical solute clusters, such that they become critical and nucleate. In the colloidal impurity heating mechanism, nanoscale solvent vapor bubbles are formed from the heat generated when impurity particles absorb incident laser light. These bubbles act as sites for heterogeneous nucleation. However, the underlying mechanism remains an open question as any one of the proposed mechanisms explains only part of the reported experimental observations. A need exists for improved technology capable of characterizing crystallization of matter using nonphotochemical laser-induced nucleation.

SUMMARY

The systems and methods described in this application relate to laser-induced nucleation in continuous flow. In conjunction with an optical field, millifluidic laser-induced nucleation can provide for a controlled nucleation process of useful products such as pharmaceuticals, drug polymorphs, and crystalline compounds. The properties of these products can be controlled and tailored through the controlled nucleation process.

The systems and methods described in this application relate to laser-induced nucleation in continuous flow. One aspect of the present disclosure is directed to a method of laser-induced nucleation in continuous flow and can include injecting at least one of a saturated solution, an undersaturated solution, or a supersaturated solution through an inlet of a device. The method can include converting the saturated solution or undersaturated solution into supersaturated solution by changing a temperature of the saturated or undersaturated solution. The method can include passing one or more laser pulses through the supersaturated solution within the device. The method can include flowing at least one of the saturated solution or the supersaturated solution or the undersaturated solution through an outlet of the device.

In some embodiments, the method includes nucleating crystals, responsive to passing the one or more laser pulses through the supersaturated solution within the device, from the supersaturated solution. The method includes collecting the crystals from the device. In some embodiments, the method includes contacting the device with a thermoelectric cooler. In some embodiments, the method includes characterizing, in situ, at least one of crystal size, shape, growth rate, number of crystals, polydispersity, or polymorphism. In some embodiments, the method includes passing the least one of the saturated solution, undersaturated solution, or supersaturated solution through a filter. In some embodiments, the method includes operating the device at a temperature above 0 K. In some embodiments, the method includes operating the device at a pressure below, above, or at 1 bar. In some embodiments, the method includes nucleating crystals from the supersaturated solution resulting from a chemical reaction such as the Heck Reaction, Suzuki Reaction, or Buchwald-Hartwig amination, or any chemical reaction carried out under conditions that result in the formation of supersaturated solution containing crystalline products or byproducts. The method includes selectively inducing nucleation in the bulk flow instead of on equipment or catalyst surfaces, thus improving solids handling.

One aspect of the present disclosure is directed to a method of laser-induced nucleation in continuous flow. The method includes providing a device. The method includes injecting a fluid through an inlet of the device. The method includes passing one or more laser pulses through the flowing fluid within the device. The method includes flowing the fluid through an outlet of the device.

In some embodiments, the flowing fluid is a single phase flow. In some embodiments, the flowing fluid is a multiphase flow. In some embodiments, the method includes nucleating crystals, responsive to passing the one or more laser pulses through the flowing fluid within the device, from a supersaturated solution. The method includes collecting the crystals from the device. In some embodiments, the method includes contacting the device with a thermoelectric cooler. In some embodiments, the method includes characterizing, in situ, at least one of crystal size, shape, growth rate, number of crystals, polydispersity, or polymorphism. In some embodiments, the method includes passing the least one of a saturated solution, undersaturated solution, or supersaturated solution through a filter. In some embodiments, the method includes operating the device at a temperature above 0 K. In some embodiments, the method includes operating the device at a pressure below, above, or at 1 bar. In some embodiments, the method includes nucleating crystals from a supersaturated solution resulting from a chemical reaction such as the Heck Reaction, Suzuki Reaction, or Buchwald-Hartwig amination, or any chemical reaction carried out under conditions that result in the formation of crystalline products or byproducts. In some embodiments, the method includes inducing nucleation in bulk flow instead of on equipment or catalyst surfaces.

DETAILED DESCRIPTION

Crystallization using batch-processing techniques can be used to concentrate and purify chemicals. However, these batch-processing techniques can face a number of challenges, such as imprecise control of the temperature profile of the batch solution. For batch solutions, heat transfer is typically driven by convective heat transfer where temperature gradients exit. Additionally, for batch solutions, it can be difficult to control the amount of fluid exposed to the laser because the fluid can diffuse or be transported away by convection. Batch crystallization methods can generate polydisperse crystal properties (e.g., size, morphology, polymorphs, number of crystals) compared to continuous-flow crystallizations.

In general, the systems and methods described in this application relate to laser-induced nucleation in continuous flow. A method of laser-induced nucleation in continuous flow includes injecting a saturated, undersaturated, or supersaturated solution through an inlet of a device. The method can include converting the saturated or undersaturated solution into supersaturated solution by changing the temperature of the saturated or undersaturated solution. The method can include passing one or more laser pulses through the supersaturated solution within the device. The method can include flowing the saturated, undersaturated, or supersaturated solution through an outlet of the device. In some embodiments, the method can include contacting the device with a thermoelectric cooler. The method can include characterizing, in situ, at least one of crystal size, shape, growth rate, polydispersity, number of crystals, and polymorphism. The method can include passing the solution through a filter. The method can control the manufacture of crystals of specific shape, growth kinetics, size, polydispersity, and polymorphs. In continuous flow, the laser and flow path can be designed to force exposure with precise control of the amount and time the liquid is exposed. In continuous flow, the amount of fluid that is not exposed to the laser can be tuned by changing the laser beam cross-section relative to the flow path cross-section. The use of two-dimensional flow can enable image analysis of particle characteristics, thus allowing for high-throughput screening applications based on, for example, machine learning and artificial intelligence. Additionally, continuous flow allows for the manipulation of multiphase flows exposed to the laser beam.

In some embodiments, the device can be a microfluidic device. The microfluidic device can be designed and fabricated for NPLIN in continuous laminar flow, which can enable real-time in situ characterization of crystal size, shape, growth rate, number of crystals, polydispersity, and polymorphism. On-chip thermoelectric cooling can create supersaturation by lowering the solution temperature. The influences of laser power density, laser exposure time, flow rate, and supersaturation can be examined for an aqueous KCl solution. The mean crystal size downstream from the irradiated region can be observed to increase with increasing supersaturation. The number of the crystals nucleated can be found to increase with increasing supersaturation and laser power density, but can be independent of the number of laser pulses to which the solution was exposed. These findings broaden the scope of nucleation in a light field by introducing a way to directly characterize the crystallization.

Referring toFIG. 1, a system for NPLIN in continuous flow is shown. The system can include a device. In the embodiments described in this application, the device is a microfluidic device. However, the present application is not limited in this regard. The device can be composed of materials that transmit laser light while maintaining intensity of the laser light. The device can be a microfluidic device102. The system100includes a continuous flow device, such as a microfluidic device102, and a laser setup104. The system100can include a solution106(e.g. a saturated solution, a supersaturated solution, a KCl saturated solution, or a KCl supersaturated solution). The solution106including a KCl saturated solution can be prepared by dissolution of KCl in deionized water. The solution106can be loaded into a syringe and filtered. The solution106can be ultrasonicated in an ultrasonic cleaner. The solution106can be filtered into clean cylindrical glass vials with screw caps.

The solution106can be loaded in a syringe and injected into the microfluidic device102by way of a syringe pump108. The syringe pump108can control the flow rate of the solution106into the microfluidic device102. The solution106can pass through a filter110before entering the microfluidic device102. The filter110can have a defined pore size (e.g., 0.2 p.m pore size). The solution106can pass through an inlet112of the microfluidic device102. The solution106can exit through an outlet114of the microfluidic device102. The solution106can pass through a nucleation zone116. The solution106can interact with laser light in the nucleation zone116. The microfluidic device102can contact a thermoelectric cooler118to promote uniform heat transfer. The thermoelectric cooler118can include a thermoelectric Peltier cooler. The microfluidic device102can contact the thermoelectric cooler118by way of a thermal paste. Heat generated on the hot side of the thermoelectric cooler118can be removed by a heat exchanger120using cold water circulation. The thermoelectric cooler118can be capable of stable sub-cooling with temperature fluctuations of less than 0.3 K. Heat transfer by the thermoelectric cooler118can be used to achieve a range of supersaturation of the solution106. The heat transfer by the thermoelectric cooler118in continuous flow can be more precise than heat transfer in batch processing.

The laser setup104can include a system to generate laser pulses. The laser pulses can be of a defined duration (e.g. 6 nanoseconds) and wavelength (e.g., 1064 nm). The laser pulses can be generated by a Q-switched Nd:YAG laser. The pulse repetition rate of the laser can be 10 pulses per second (pps) or a submultiple of 10 pps. For example, the pulse repetition rate can be 10 pps, 2 pps, or a single shot). The laser beam of the laser pulse can be linearly polarized. The laser beam of the laser pulse can be linearly polarized using a Glan-Taylor polarizer, or any polarizer which can work effectively at higher laser powers without being damaged. Average power of the laser pulse can be measured with a power meter. Average power measurements can allow for the calculation of the peak power density. The continuous variation of the laser power density can be achieved by rotating a half-wave retardation plate. The laser can be matched with the geometry of the device. For example, the cross-section of the device can be designed to operate with the laser beam. The laser beam can also be circularly or elliptically polarized. The laser can also be at any wavelength that is not absorbed by the solution.

The crystallization of the solution106can be monitored by a camera mounted on a microscope122. The camera can be connected to a 13-inch screen to provide an equivalent magnification of 145.6× and a resolution of 0.92 μm per pixel. The camera can be focused at a depth of 400 μm below the glass microscope slide212of the microfluidic device102.

Referring toFIG. 2, a microfluidic system is shown. The microfluidic system200can include a microfluidic device102. The microfluidic device102can include a polydimethylsiloxane (PDMS) layer210positioned between two solid surfaces, such as glass microscope slides212, after a surface plasma treatment. The microfluidic device102can be composed of material that would allow transmission of the laser (e.g., glass, borosilicate, fused silica) and materials that the laser does not need to pass through (e.g., silicon, metal, silicon carbide, ceramics, polymers). The materials can operate over extended periods of time while being exposed to the laser. The polymers can include PDMS, fluorinated polymers, polycarbonate, PEEK, PTFE, PFA, FEP, Teflon®, Teflon® AF). The surface plasma treatment can include PDC-001-HP with Harrick Plasma. The PDMS layer210can be fabricated by curing Sylgard184in a 3D-printed mold. The microfluidic device102can have a length of 75 mm and a width of 25 mm. The microfluidic device102can have dimensions that enable laminar flow. The microfluidic device102can have dimensions that enable turbulent flow. Laminar flow and turbulent flow can be defined by the calculation of Reynolds numbers. For example, laminar flow can be defined by a Reynolds number of less than 2300. Turbulent flow can be defined by a Reynolds number of greater than 4000. The dimensions of the microfluidic device102can have dimensions that enable a flow in a transition regime. The transition regime can be defined by a Reynolds number of between 2300 and 4000. The device can have dimensions that depend on the desired (e.g., target) throughput or production rate. For example, the device can have dimensions that depend on a volume per time or mass per time. The microfluidic device102can include a channel214. The channel214can have a cross-section of 1 mm×0.79 mm. The channel214can have a total length of 125 mm. The microfluidic device102can include a nucleation zone116. The nucleation zone116can have a diameter of 1 mm. The solution106can interact with laser light in the nucleation zone116. The microfluidic device102can have a volume of 99 μL. The microfluidic device102can be composed of materials that minimally or do not scatter light upon exposure to laser light. The inlet112can be located above the outlet114. The inlet can allow the solution106to pass through the channel214. The channel214can be disposed along the length of the microfluidic device102. The channel214can define an axis that is perpendicular to an axis defined by the nucleation zone116. The solution106can flow through the channel214along a fluid flow path that enters through the inlet112and exits through the outlet114of the microfluidic device102.

Referring toFIG. 3, a laser setup is shown. The laser setup300can include the laser setup104. The laser setup300can include a laser302. The laser302can be a Nd:YAG laser. The laser302can be aligned to cause NPLIN. The laser302can emit a train of 1064-nm light pulses that are directed into the nucleation zone116of the microfluidic device102. The wavelength of the laser302can be a wavelength that is not absorbed by the solution106. The wavelength of the laser302can be a wavelength that is not absorbed by a solute in the solution106. For example, the wavelength of the laser302can be in visible light range. The wavelength of the laser302can be in the near infrared range. The direction of the light pulses can be controlled using mirrors304and a right angle prism306. The intensity of the laser can be adjusted by rotating a half-wave plate308. The diameter of the laser can be controlled using two circular ceramic apertures310. The laser beam of the laser pulse can be linearly polarized. The laser beam of the laser pulse can be linearly polarized using a polarizer312(e.g., a Glan Taylor polarizer). The laser pulses can have a pulse duration. The pulse duration can range from milliseconds to femtoseconds. For example, the pulse duration can be nanoseconds (e.g. 6 nanoseconds).

Referring toFIG. 4, a relationship between sub-cooling temperature and supersaturation400is shown. For example, the sub-cooling temperature of supersaturated KCl solutions with supersaturations of 1.06, 1.08, and 1.10 were calculated. An increasing sub-cooling temperature is correlated with an increasing supersaturation. Microfluidics can allow for fast conductive heat transfer, thereby allowing for supersaturation to be achieved before the KCl solution reaches the nucleation zone at a flow rate of 200 μL/min.

Referring toFIG. 5, a temperature profile along a channel of a microfluidic device is shown. The microfluidic device102can be divided into five zones: inlet112, supersaturation zone502, nucleation zone116, post-nucleation zone506, and outlet114. A stable temperature profile is created near the nucleation zone116with small temperature fluctuations of 0.1 K. The microfluidic device102can be designed such that the temperature of the microfluidic device102rises and supersaturation decreases while the solution106approaches the outlet114. Therefore, further crystal growth can be inhibited and any potential clogging downstream can be avoided.

Referring toFIG. 6, a system for microfluidic nonphotochemical laser-induced nucleation is shown.FIG. 6Ashows a supersaturated KCl solution with supersaturation of 1.06 stirred for over 12 hours showing no trace of nucleation or crystals.FIG. 6Bshows the microfluidic device102.FIG. 6Cshows a supersaturated KCl solution flowing through the nucleation zone116with no observed nucleation without laser irradiation.FIG. 6Dshows a supersaturated KCl solution flowing through the channel214of the microfluidic device102with no observed crystals.FIG. 6Eshows that, with laser irradiation at 200 MW/cm2, crystal grew too large and too fast using a flow rate of 50 μm/min and clogged the nucleation zone116.FIG. 6Fshows that, with laser irradiation at 200 MW/cm2, crystals were flowing through the channel214of the microfluidic device102at a flow rate of 200 μm/min. The channel walls602are shown inFIGS. 6C, 6D, and 6E.

Referring toFIG. 7, a relationship700between crystal size distribution and supersaturation is shown.FIG. 7Ashows a plot of crystal size distribution vs. supersaturation, S of 1.06, 1.08, and, 1.10, incorporating data at all intensities.FIG. 7Bshows a plot of number of crystals vs. laser power density at supersaturations of 1.06, 1.08, and 1.10.FIG. 7Cshows a zoomed-in view ofFIG. 7Bat lower laser power density. Error bars represent standard deviations from averaging the results of three experiments at each intensity. Straight-line fits to the data are shown as solid lines forFIG. 7BandFIG. 7C.FIG. 7Bshows a plot of the average number of crystals nucleated, Ncrystal, vs. laser intensity, I, for different supersaturations and number of pulses. The experiments were carried out at a constant flow rate of 200 μL/min, so that irradiated solution volume is proportional to the flow time. The values of NcrystalinFIG. 7Bhave been normalized to a flow time of 1 minute. The observed unimodal distribution of crystal sizes is evidence of the absence of secondary nucleation. The number of crystals formed is approximately proportional to the laser intensity, but with an offset owing to the intensity threshold. The best linear fits are included forFIG. 7BandFIG. 7C.

The laser-induced nucleation experimental results under different supersaturations, laser intensities and laser pulse repetition rates are reported in Table 1. Details of Ncrystaland the normalization method are shown in Table 1 where the video time is the residence time.

The threshold power densities for NPLIN are reported in Table 2. The fitted parameters at different supersaturations and laser repetition rates using Ncrystal=m(I−Ith).

FIG. 8illustrates a method for laser-induced nucleation in continuous flow according to an embodiment. In brief overview, the method800may include injecting a solution through an inlet of a device (BLOCK802). The method800may include converting the saturated or undersaturated solution into supersaturated solution (BLOCK804). The method800may include passing one or more laser pulses through the supersaturated solution (BLOCK806). The method800may include flowing the solution through an outlet of the device (BLOCK808). The method800may include characterizing the resulting crystals (BLOCK810).

The method800may include injecting a solution through an inlet of a device (BLOCK802). The solution can be a saturated solution, undersaturated solution, or a supersaturated solution. The device can be a microfluidic device. The solution can pass through an inlet of the microfluidic device. The inlet may be located above the outlet. The inlet may be located below the outlet. The device can be operated at extreme temperatures. For example, the device can be operated at a temperature above 0 K. The device can be operated at cryogenic temperatures. The device can be operated at temperatures hundreds of degrees above ambient temperature (e.g., 100° C., 200° C., 300° C., 400° C., 500° C.). The device can be operated at high pressures (e.g., 10 bar, 50 bar, 100 bar, 200 bar, 500 bar). The device can be operated at pressures below, above, or at 1 bar. The method can include injecting a flow through an inlet of the device. The flow can include a single phase flow. For example, the flow can include a liquid, gas, supercritical fluid, or any combinations thereof. The flow can include a multiphase flow. For example, the multiphase flow can include a two-phase flow (e.g., gas-liquid flow, gas-solid flow, liquid-liquid flow, liquid-solid flow). The multiphase flow can include a three-phase flow (e.g., gas-liquid-solid flow, gas-liquid-liquid flow, solid-liquid-liquid flow).

The method800may include converting the saturated or undersaturated solution into supersaturated solution (BLOCK804). The method can include converting the saturated or undersaturated solution into supersaturated solution by changing a temperature of the saturated or undersaturated solution. For example, the method can include using a thermoelectric cooler to convert the saturated or undersaturated solution into supersaturated solution. The method can include causing a temperature change by a thermoelectric cooler.

The method800may include passing one or more laser pulses through the supersaturated solution (BLOCK806). The laser pulses can be generated by a Q-switched Nd:YAG laser. The pulse repetition rate of the laser can be 10 pulses per second (pps) or a submultiple of 10 pps. For example, the pulse repetition rate can be 10 pps, 2 pps, or a single shot). The pulsed laser beam can be linearly polarized, circularly polarized, or elliptically polarized. The laser beam of the laser pulse can be linearly polarized using a Glan Taylor polarizer. A quarter wave plate can be used to transform a linearly polarized beam into a circularly or elliptically polarized beam. Average power of the laser pulse can be measured with a Coherent LM30V power meter. Average power measurements can allow for the calculation of the peak power density. The continuous variation of the laser power density can be achieved by rotating a half-wave retardation plate.

The method800may include flowing the saturated, undersaturated, or supersaturated solution out of a device (BLOCK808). The method can include flowing the solution through an outlet of the device. The device can include a microfluidic device. The solution can exit through an outlet of the microfluidic device. The outlet may be located below the inlet112. The outlet may be located above the inlet, or the outlet and inlet may be side-by-side. The device can handle crystals or solids.

The method800may include characterizing the resulting crystals (BLOCK810). The method800can include imaging the resulting crystals. The method800can include characterizing the resulting crystals before flowing the solution through an outlet of the device. The method800can include imaging the resulting crystals before flowing the solution through an outlet of the device. The method800can include characterizing the resulting crystals after flowing the solution through an outlet of the device. The method800can include imaging the resulting crystals after flowing the solution through an outlet of the device.

In some embodiments, the method800can include nucleating crystals. Nucleating crystals can be responsive to passing the one or more laser pulses through the supersaturated solution within the device. The method can include nucleating crystals from the supersaturated solution. The method can include collecting the crystals from the device. The method can include nucleating crystals from the supersaturated solution formed by a reaction (e.g., Heck Reaction, Suzuki Reaction, or Buchwald-Hartwig amination). The method can include nucleating crystals from the supersaturated solution resulting from a chemical reaction such as the Heck Reaction, Suzuki Reaction, or Buchwald-Hartwig amination, or any chemical reaction carried out under conditions that result in the formation of crystalline products or byproducts.

In some embodiments, the method can improve solids handling in continuous flow. The method can include selectively inducing the nucleation of crystals in the bulk flowing fluid instead of on equipment or catalyst surfaces. For example, the nucleation can include homogeneous nucleation as opposed to heterogeneous nucleation. The method can include nucleating crystals that flow through equipment or catalysts without any solids accumulation that may result from their flocculation, aggregation, deposition, hydrodynamic bridging, inertial impaction, dendrite formation, or heterogeneous nucleation.

Referring toFIG. 9, an embodiment of computational fluid dynamics (CFD) modeling900of the microfluidic system is shown. In an embodiment, the CFD simulation was carried out using COMSOL Multiphysics® version 5.3 (Build:316). Geometries were created with dimensions identical to those of the actual microfluidic device102and thermoelectric cooler118. Corning 7740 (Pyrex), water, structural steel, and PDMS were assigned as material to the glass layer, fluid, cooler, and middle layer, respectively. A relative tolerance of 0.001 was used in stationary studies. The microfluidic device body and cooler used a normal-sized mesh while the fluid used a finer mesh calibrated for fluid dynamics calculation.FIG. 9Ashows the mesh used in the CFD calculations.FIG. 9Bshows the temperature field simulation results.

Referring toFIG. 10, an embodiment of a temperature map1000of the microfluidic system is shown. The thermocouple (zone a) has an average temperature of 12.08±0.34° C. The microfluidic device102surface above the channel (zone b) has an average temperature of 12.29±0.44° C. The temperature map was measured using an infrared camera (ICI P9000).

Referring toFIG. 12, an embodiment of plots of crystal size distribution1200is shown. Plots of crystal size distribution at 1.06 supersaturation are shown.FIG. 12Ashows a plot of crystal size distribution at 100 MW/cm2and 5 minutes.FIG. 12Bshows a plot of crystal size distribution at 50 MW/cm2and 5 minutes.FIG. 12Cshows a plot of crystal size distribution at 20 MW/cm2and 15 minutes.FIG. 12Dshows a plot of crystal size distribution at 10 MW/cm2and 15 minutes.

As shown inFIG. 13, e.g., a computer-accessible medium1320(e.g., as described herein, a storage device such as a hard disk, floppy disk, memory stick, CD-ROM, RAM, ROM, etc., or a collection thereof) can be provided (e.g., in communication with the processing arrangement1310). The computer-accessible medium1320may be a non-transitory computer-accessible medium. The computer-accessible medium1320can contain executable instructions1330thereon. In addition or alternatively, a storage arrangement1340can be provided separately from the computer-accessible medium1320, which can provide the instructions to the processing arrangement1310so as to configure the processing arrangement to execute certain exemplary procedures, processes and methods, as described herein, for example. The computer-accessible medium1320can contain memory1360, which can provide storage for information. The computer-accessible medium1320can contain an I/O port1350, which can provide an interface between the computer-accessible medium1320and other devices. The instructions may include a plurality of sets of instructions.

Software and web implementations of the present invention could be accomplished with standard programming techniques with rule based logic and other logic to accomplish the various database searching steps, correlation steps, comparison steps and decision steps. It should also be noted that the words “component” and “module,” as used herein and in the claims, are intended to encompass implementations using one or more lines of software code, and/or hardware implementations, and/or equipment for receiving manual inputs.

With respect to the use of substantially any plural and/or singular terms herein, those having skill in the art can translate from the plural to the singular and/or from the singular to the plural as is appropriate to the context and/or application. The various singular/plural permutations may be expressly set forth herein for the sake of clarity. In some cases, the actions recited in the claims can be performed in a different order and still achieve desirable results. In addition, the processes depicted in the accompanying figures do not necessarily require the particular order shown, or sequential order, to achieve desirable results. In certain implementations, multitasking and parallel processing may be advantageous. Thus, particular implementations of the invention have been described.

The foregoing description of illustrative embodiments has been presented for purposes of illustration and of description. It is not intended to be exhaustive or limiting with respect to the precise form disclosed, and modifications and variations are possible in light of the above teachings or may be acquired from practice of the disclosed embodiments. Therefore, the above embodiments should not be taken as limiting the scope of the invention.